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Background 5-aminolevulinic acid (5-ALA) fluorescence-guided resection increases the percentage of complete CNS tumor resections and improves the progression-free survival of IDH-wildtype glioblastoma patients. A small subset of IDH-wildtype glioblastoma shows no 5-ALA fluorescence. An explanation for these cases is missing. In this study, we used DNA methylation profiling to further characterize non-fluorescent glioblastomas. Methods Patients with newly diagnosed and recurrent IDH-wildtype glioblastoma that underwent surgery were analyzed. The intensity of intraoperative 5-ALA fluorescence was categorized as non-visible or visible. DNA was extracted from tumors and genome-wide DNA methylation patterns were analyzed using Illumina EPIC (850k) arrays. Furthermore, 5-ALA intensity was measured by flow cytometry on human gliomasphere lines (BT112 and BT145). Results Of 74 included patients, 12 (16.2%) patients had a non-fluorescent glioblastoma, which were compared to 62 glioblastomas with 5-ALA fluorescence. Clinical characteristics were equally distributed between both groups. We did not find significant differences between DNA methylation subclasses and 5-ALA fluorescence (P = .24). The distribution of cells of the tumor microenvironment was not significantly different between the non-fluorescent and fluorescent tumors. Copy number variations in EGFR and simultaneous EGFRvIII expression were strongly associated with 5-ALA fluorescence since all non-fluorescent glioblastomas were EGFR-amplified (P < .01). This finding was also demonstrated in recurrent tumors. Similarly, EGFR-amplified glioblastoma cell lines showed no 5-ALA fluorescence after 24 h of incubation. Conclusions Our study demonstrates an association between non-fluorescent IDH-wildtype glioblastomas and EGFR gene amplification which should be taken into consideration for recurrent surgery and future studies investigating EGFR-amplified gliomas.

Background Seizures can present at any time before or after the diagnosis of a glioma. Roughly, 25%–30% of glioblastoma (GBM) patients initially present with seizures, and an additional 30% develop seizures during the course of the disease. Early studies failed to show an effect of general administration of antiepileptic drugs for glioblastoma patients, since they were unable to stratify patients into high- or low-risk seizure groups. Methods 111 patients, who underwent surgery for a GBM, were included. Genome-wide DNA methylation profiling was performed, before methylation subclasses and copy number changes inferred from methylation data were correlated with clinical characteristics. Independently, global gene expression was analyzed in GBM methylation subclasses from TCGA datasets (n = 68). Results Receptor tyrosine Kinase (RTK) II GBM showed a significantly higher incidence of seizures than RTK I and mesenchymal (MES) GBM (P < .01). Accordingly, RNA expression datasets revealed an upregulation of genes involved in neurotransmitter synapses and vesicle transport in RTK II glioblastomas. In a multivariate analysis, temporal location (P = .02, OR 5.69) and RTK II (P = .03, OR 5.01) were most predictive for preoperative seizures. During postoperative follow-up, only RTK II remained significantly associated with the development of seizures (P < .01, OR 8.23). Consequently, the need for antiepileptic medication and its increase due to treatment failure was highly associated with the RTK II methylation subclass (P < .01). Conclusion Our study shows a strong correlation of RTK II glioblastomas with preoperative and long-term seizures. These results underline the benefit of molecular glioblastoma profiling with important implications for postoperative seizure control.

In recent years, 3D4K exoscope systems (EXs) have been introduced to microneurosurgery and reported to be an alternative to conventional operating microscopes (OMs). This study reviews our single-center experience using an 3D4K EX in intracranial aneurysm surgery.To investigate the applicability of a novel 3D4K EX for intracranial aneurysm surgery.A retrospective analysis of patients who underwent microsurgical repair of incidentally or ruptured cerebral aneurysms between August 2018 and August 2020 was performed. Patient and aneurysm characteristics and technical features, including 3-dimensional indocyanine green fluorescence, were evaluated. Data on surgery duration were statically assessed for a time trend and comparability with the OM cohort.Overall, we collected 185 aneurysm cases in which the exoscope was used in 44 cases. The mean duration of surgery using the EX was in similar range to those using the OM (165.5 ± 45.8 minutes vs 160.5 ± 39.2 minutes, P.05). Routine postoperative computed tomography angiography showed comparable rates of complete aneurysm occlusion (95.5% vs 92.2%, P.05) and postoperative complications (9.1% vs 9.7%, P.05). There was no necessity to revert to the OM from the EX. Three-dimensional indocyanine green fluorescence was used in all procedures without any malfunction.The 3D4K EX for vascular microsurgical cases proved to be as useful as the OM. Because of the ease of use and comparable surgical results, the EX has the potential to become an accepted and additional visualization tool in vascular microsurgery next to the OM.

Background: The Comprehensive Complication Index (CCI) is a numerical scale based on the Clavien-Dindo classification (CDC) and both are widely used to assess outcome. However, the CCI had not been described for neurosurgical procedures. Objective: We aimed to investigate the value of the CCI to predict outcome in patients who underwent elective intracranial surgery. Methods: Prospective cohort study including patients who underwent elective intracranial surgery. Complications were graded using CDC, and the CCI was calculated daily. Neurological outcome was assessed using mRS, NANO, NIHSS, and KPS. Results: Of 294 patients who underwent an elective intracranial procedure, 211 (71.8%) patients underwent a craniotomy, while 28 (9.5%) patients had a burr hole procedure and 55 (18.7%) patients a transsphenoidal approach. A higher blood loss was the only significant predictor for a higher CCI (OR 1.09, 95% CI 1.00-1.12, P < 0.01). Patients with a higher CCI had a longer LOS (mean: 5.4 versus 10.9 days, P < 0.01) and ICU stay (mean: 0.8 versus 2.4 days, P < 0.01). Daily CCI revealed a risk for complications after craniotomies until postoperative day (POD) 7. In patients who underwent brain tumor surgery, the resection of meningiomas and metastasis showed a similar developmental course of CCI. A significantly higher CCI was observed in patients who had a neurological deterioration at discharge ( P < 0.01). Conclusion: CCI is a valid scale to measure outcome after intracranial procedures and correlates with neurological outcome. Risk for adverse events after craniotomy is at highest until postoperative day 7.

Background Complex liver resection is a risk factor for the development of AKI, which is associated with increased morbidity and mortality. Aim of this study was to assess risk factors for acute kidney injury (AKI) and its impact on outcome for patients undergoing complex liver surgery. Methods AKI was defined according to the KDIGO criteria. Primary endpoint was the occurrence of AKI after liver resection. Secondary endpoints were complications and mortality. Results Overall, 146 patients undergoing extended liver resection were included in the study. The incidence of AKI was 21%. The incidence of chronic kidney disease (CKD) and hepatocellular carcinoma were significantly higher in patients with AKI. In the AKI group, the proportion of extended right hepatectomies was the highest (53%), followed by ALPPS (43%). Increased intraoperative blood loss, increased postoperative complications and perioperative mortality was associated with AKI. Besides age and CKD, ALPPS was an independent risk factor for postoperative AKI. A small future liver remnant seemed to increase the risk of AKI in patients undergoing ALPPS. Conclusion Following extended liver resection, AKI is associated with an increased morbidity and mortality. ALPPS is a major independent risk factor for the development of AKI and a sufficient future liver remnant could avoid postoperative AKI.

Background Transcriptional enhanced associated domain (TEAD) transcription factors are nuclear effectors of several oncogenic signalling pathways including Hippo, WNT, TGF-s and EGFR pathways that interact with various cancer genes. The subcellular localization of TEAD regulates the functional output of these pathways affecting tumour progression and patient outcome. However, the impact of the TEAD family on pancreatic ductal adenocarcinoma (PDAC) and its clinical progression remain elusive. Methods A cohort of 81 PDAC patients who had undergone surgery was established. Cytoplasmic and nuclear localization of TEAD1, TEAD2, TEAD3 and TEAD4 was evaluated with the immunoreactive score (IRS) by immunohistochemistry (IHC) using paraffin-embedded tissue. Results were correlated with clinicopathological data, disease-free and overall survival. Results Nuclear staining of all four TEADs was increased in pancreatic cancer tissue. Patients suffering from metastatic disease at time of surgery showed a strong nuclear staining of TEAD2 and TEAD3 (p cytoplasmic ratio of TEAD2 and TEAD3 was associated with a shorter overall survival and TEAD2 emerged as an independent prognostic factor for disease-free survival. Conclusion Our study underlines the importance of TEAD transcription factors in PDAC as a nuclear localization was found to be associated with metastatic disease and an unfavourable prognosis after surgical resection.

Purpose Few studies reported about the potential of unphosphorylated heat shock protein 27 (HSP27) and phosphorylated heat shock protein 27 (pHSP27) as a predictor for survival and gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC). In this study, we analysed the expression patterns of pHSP27 and HSP27 in a patient population after surgery and correlated the immunohistochemical results with clinicopathological data and long-term outcome of the patients. Methods HSP27 and pHSP27 (Ser-15, Ser-78 and Ser-82) protein expression were analysed by immunohistochemistry using the immunoreactive score (IRS) from paraffin-embedded tissue of 106 patients with PDAC who underwent surgery. Immunohistochemical results were correlated with clinicopathological data, disease-free (DFS) and overall survival (OS). Results HSP27 expression was significantly lower in patients with a shorter OS (p = 0.006) and DFS (p p = 0.001). Furthermore, HSP27 was downregulated in patients suffering from metastases at time of surgery (p p = 0.007). In contrast, pHSP27-Ser15, -Ser78 and -Ser82 were not associated with any survival data of the study population. Conclusion HSP27 seems to be a strong indicator for the prediction of OS and DFS. Moreover, HSP27 could play a role in the formation and migration of liver metastases of PDAC.

Background DNA methylation-based tumor classification allows an enhanced distinction into subgroups of glioblastoma. However, the clinical benefit of DNA methylation-based stratification of glioblastomas remains inconclusive. Methods Multicentric cohort study including 430 patients with newly diagnosed glioblastoma subjected to global DNA methylation profiling. Outcome measures included overall survival (OS), progression-free survival (PFS), prognostic relevance of EOR and MGMT promoter methylation status as well as a surgical benefit for recurrent glioblastoma. Results 345 patients (80.2%) fulfilled the inclusion criteria and 305 patients received combined adjuvant therapy. DNA methylation subclasses RTK I, RTK II, and mesenchymal (MES) revealed no significant survival differences (RTK I: Ref.; RTK II: HR 0.9 [95% CI, 0.64–1.28]; p = 0.56; MES: 0.69 [0.47–1.02]; p = 0.06). Patients with RTK I (GTR/near GTR: Ref.; PR: HR 2.87 [95% CI, 1.36–6.08]; p < 0.01) or RTK II (GTR/near GTR: Ref.; PR: HR 5.09 [95% CI, 2.80–9.26]; p < 0.01) tumors who underwent gross-total resection (GTR) or near GTR had a longer OS and PFS than partially resected patients. The MES subclass showed no survival benefit for a maximized EOR (GTR/near GTR: Ref.; PR: HR 1.45 [95% CI, 0.68–3.09]; p = 0.33). Therapy response predictive value of MGMT promoter methylation was evident for RTK I (HR 0.37 [95% CI, 0.19–0.71]; p < 0.01) and RTK II (HR 0.56 [95% CI, 0.34–0.91]; p = 0.02) but not the MES subclass (HR 0.52 [95% CI, 0.27–1.02]; p = 0.06). For local recurrence (n = 112), re-resection conveyed a progression-to-overall survival (POS) benefit (p < 0.01), which was evident in RTK I (p = 0.03) and RTK II (p < 0.01) tumors, but not in MES tumors (p = 0.33). Conclusion We demonstrate a survival benefit from maximized EOR for newly diagnosed and recurrent glioblastomas of the RTK I and RTK II but not the MES subclass. Hence, it needs to be debated whether the MES subclass should be treated with maximal surgical resection, especially when located in eloquent areas and at time of recurrence.

INTRODUCTION The CeTeG/NOA-09 trial demonstrated superior median overall survival (mOS, 48.1 months) in MGMT-methylated glioblastoma treated with lomustine/temozolomide compared to temozolomide. We retrospectively analyzed an off-study cohort of patients treated with lomustine/temozolomide to gather real-world data on this new regimen. METHODS Adult patients from 20 centers in Germany, Austria and Switzerland were included. Inclusion criteria were MGMT-methylated IDHwt glioblastoma newly diagnosed prior to end of 2020, and lomustine/temozolomide treatment as part of first-line therapy. RESULTS 321 patients with a median age of 57 years (range, 21-78) and a median follow-up of 19.9 months were included. In the whole cohort, mOS was 41.0 months (95%CI, 33.0 – not reached). In patients starting lomustine/temozolomide immediately upon initiation of radiotherapy strictly following the CeTeG protocol (88%), mOS was 52.8 months (35.8 – not reached) as compared to 24.6 months (17.6 – not reached) in patients starting lomustine/temozolomide after completion of radiotherapy/concomitant temozolomide (12%, logrank test: p = 0.06). Patients with a KPS < 80 had a shorter mOS of 19.7 months (95%CI, 16.6 – not reached) compared to 41.0 months (33.0 – not reached, p = 0.009) in KPS 80-100. Gross total resection (GTR, 53.9%) was associated with longer mOS (52.8 months, 95%CI 24.1 – not reached) compared to partial resection/biopsy (30.5 months, 95%CI 36.8 – not reached, p=0.004). Multivariable Cox regression analysis confirmed GTR (HR 0.66, p = 0.033) and younger age ( ≤ 50 years: HR 0.42, p = 0.001), but not KPS (80-100 vs. lower: HR 0.66, p = 0.12) as independent prognostic factors. DISCUSSION In this real-world multicenter cohort, survival was similar to the promising results of CeTeG/NOA-09. Further analyses should investigate a potentially reduced benefit from lomustine/temozolomide in patients with low KPS/no GTR and a possible detrimental effect from deferred lomustine/temozolomide initiation. The median follow-up is admittedly short, updated data will be presented.

DNA methylation-based tumor classification allows an enhanced distinction into subgroups of glioblastoma. However, the clinical benefit of DNA methylation-based stratification of glioblastomas remains inconclusive. We performed a multicentric cohort study including 430 patients with newly diagnosed glioblastoma whose tumors were subjected to DNA methylation profiling. The primary outcome was overall survival (OS) and progression-free survival (PFS). Secondary outcomes were the prognostic relevance of EOR and MGMTpromoter methylation status as well as surgical benefit for recurrent glioblastoma. After stratifying patients in accordance with their DNA methylation subclasses RTK I, RTK II, and mesenchymal (MES), outcome analyses revealed no significant differences between these three methylation subclasses (p = 0.06). RTK I or RTK II tumors who underwent gross-total resection (GTR) or near GTR had a longer OS and PFS than partially resected patients (p < 0.01). In the MES subclass, no survival benefit for a maximized EOR was found (p = 0.33). In multivariate analysis, the therapy response-predictive value of MGMT promoter methylation was evident for RTK I (p < 0.01) and RTK II (p = 0.02) but failed to be an independent factor in the MES subclass (p= 0.06). For local recurrence, re-resection conveyed a progression-to-overall survival (POS) benefit (p < 0.01), which was evident in the RTK I (p = 0.03) and RTK II (p < 0.01) subclasses, but not in the MES subclass (p = 0.33).This study demonstrates a survival benefit from maximized EOR at surgery for newly diagnosed and recurrent glioblastomas of the RTK I and RTK II subclass but not the MES subclass. Hence, it needs to be carefully considered whether the MES subclass should be treated with maximal surgical resection, especially when located in eloquent areas and at time of recurrence.

DNA methylation-based classification of central nervous system tumours has been increasing in importance for routine clinical workups and offers novel opportunities in discriminating subtypes which could lead to a more customized therapy. However, there are still unclassifiable entities for which defining an effective therapeutic regimen is challenging. The aim of our study was to gain further insight in these challenging cases. We included 81 patients with a calibrated score below 0.9 in the classifier output, who underwent surgery for a tumour of the central nervous system (CNS). 47 patients had a different output using the classifier version v11b4 when compared to their histological diagnosis. Of these, 41 patients (87.2 %) did not have any diagnosis from the methylation classifier (“no matching methylation class”). Surgical and clinicopathological features as well as DNA input had no impact on the calibrated score. Cases with non-classifiable tumors had a significantly longer time until a decision for adjuvant therapy and these cases were presented more often in neurooncological tumor boards (p< 0.01). Further analyses in 23 glioblastoma patients revealed comparable results for the overall survival, but a significantly shorter progression-free survival in cases with a discrepancy between the histological and classifier diagnosis. Application of the latest classifier version v12.5 enabled classification in 67.9% of cases, resulting in re-classification with a high calibrated score (> 0.9) in 25.7% of the tumors. Taken together, our study presents unclassifiable cases and the possible clinical impact when waiting for the accurate diagnosis in these challenging cases. Even though DNA methylation profiling significantly contributes to advanced CNS tumour diagnostics, clinicians should be aware of a prolonged interval to treatment initiation, especially for highly malignant brain tumours. Therefore, we would recommend to schedule adjuvant treatment as early as possible if surgical and histological results are suspicious for this disease.

OBJECTIVE Extracellular vesicles (EVs) represent a population of lipid bilayer nanoparticles released by all cell types, including tumor cells that can serve as a noninvasive source for liquid biopsy. To date, MRI images have been the established method for monitoring treatment efficacy in brain tumor patients. We investigated the potential of pure EV count for diagnosis, prognosis, and treatment monitoring in gliomas. METHODS Plasma samples, differential blood counts, at multiple timepoints before and after surgery of glioblastoma patients (n=101) were collected. Follow-up samples were obtained every 3 months. Healthy donors served as controls (n=29). Plasma EVs concentration was measured by Nanoparticle Tracking Analysis (NTA). EVs were characterized by electron microscopy and imaging flow cytometry. Tumor burden was measured by MRI images. Clinical characteristics were prospectively recorderd. In addition plasma EVs from Mut3 tumor bearing mice were analysed at d3, d5, d7, d10, d12 after tumor injection (n=20). MRI images and differential blood counts were analyzed. RESULTS Glioblatoma patients have a 5-fold increase of plasma EVs compared to HD; p < 0.0001). Circulating EVs counts correlated only with FLAIR hyperintensity and with no other MRI or blood-based parameter. Similar results were obtained from Mut3 tumor mice. Dichotomisation of GBM patients in EVhigh and low revealed a significant overall survival and progression free survival benefit for EVlow patients (p=0.004). After surgery, EVs decreased significantly (5-fold, p< 0.0001). A massive drop in EVs was associated with gross-total resection (p < 0.05). At the time of tumor recurrence, the number of circulating EVs increased in all patients during a follow-up (9 months). CONCLUSION Our findings highlight the potential of circulating EVs as a biomarker tool for diagnosis, prognosis and treatment monitoring in GBM patietns, as they seem to reflect the presence of a tumor mass and thus may assist in clinical decision making.

Benchmarks are important to measure and aid in improve outcomes for surgical procedures. However, best achievable results that have been validated internationally for transsphenoidal surgery are not available. Therefore, we aimed to establish robust, standardized outcome benchmarks for transsphenoidal surgery of pituitary adenomas. A total of 2862 transsphenoidal tumor resections from 12 high-volume centers in 4 continents were analyzed. Patients were risk stratified and the median values of each center’s outcomes were established. The outcome benchmark was defined as the 75th percentile of all median values for a particular outcome as defined by Staiger et al. Out of 2862 patients, 1201 (41.9%) defined the benchmark cohort. The proportion of benchmark cases contributing to the final cohort ranged across centers between 22.1% to 59.7%. Within the benchmark cases, 928 (73.3%) patients underwent microscopic (MTS) and 263 (21.9%) patients endoscopic endonasal resection (EES). The overall postoperative complication rate was 18.9% with an in-hospital mortality between 0.0-0.8%. Benchmark cutoffs were ≤ 3.3% for reoperation rate, ≤ 4.6% for cerebrospinal fluid leak requiring intervention, and ≤ 15.3% for transient diabetes insipidus. At 6 months follow-up, benchmark cutoffs were calculated as follows: readmission rate: ≤ 7.1%, new hypopituitarism ≤ 15.5%, new neurological deficit ≤ 1.2%, tumor remnant ≤ 25.5%. This analysis defines benchmark values for transsphenoidal resection of pituitary adenomas targeting morbidity, mortality, surgical and tumor-related outcomes. The benchmark cutoffs can be used to assess different centers, patients’ populations, and novel surgical techniques.

BACKGROUND Seizures are a common symptom of patients suffering from glioblastoma and there is evidence that these tumours are morphologically different. However, the relationship of DNA methylation and glioblastoma-related seizures has not been well characterized. Only one study described an amplification of genes encoding receptor tyrosine kinases (RTK) as a positive predictor for intraoperative seizures during craniotomy. METHODS 59 patients who underwent surgery with confirmed IDH-wildtype glioblastoma, WHO grade 4, were included. Genome-wide DNA methylation profiling was performed using an 850k Illumina EPIC array and classified by the DKFZ brain tumor classifier. Methylation glioblastoma subclasses and gene alterations were correlated with clinical characteristics including preoperative and long-term seizures. RESULTS Overall, 18 of 59 patients (30.5%) presented with seizures of whom suffered 8 (44.4%) from a focal and 10 (55.6%) from a generalized seizure. Correlation of preoperative seizures with glioblastoma subclasses and DNA genes identified a higher incidence of preoperative seizures in patients with the glioblastoma subclass of receptor tyrosine kinase II (RTK; EGFR amplified) (p=0.031). In addition, these patients were more likely to present with generalized seizures (p=0.05). In multivariate analysis, temporal location (p=0.014, OR 5.785) but moreover RTK II (p=0.024, OR 7.052) was most predictive for preoperative seizures. Furthermore, recurrent seizures with an increased antiepileptic medication at last follow-up (mean: 9.2 months) occurred more often in RTK II-glioblastoma (p< 0.05). Kaplan-Meier curves showed no significant association between the presentation of seizures and overall or progression-free survival. In addition, further survival analyses did not reveal a correlation of methylation glioblastoma subgroups with the outcome. CONCLUSION Our study showed a strong correlation of the RTK II methylation subclass with preoperative and long-term seizures in patients suffering from glioblastoma.

OBJECTIVE: Outcome measuring is increasingly important in neurosurgery. Recently, a classification for assessing Intraoperative adverse events (iAE) was introduced (ClassIntra). We aimed to analyze the reliability of the ClassIntra to reflect Intraoperative complications and the potential to predict the outcome of pediatric and adolescent patients who underwent resection of CNS neoplasms. METHODS: A prospective study between 01 July and 31 December 2021 was conducted. The ClassIntra grade for each tumor resection was evaluated at sign-out (Grade 0 to V). Postoperative complications were graded after Clavien-Dindo and Comprehensive Complication Index (CCI). Neurological status was assessed prior surgery and at discharge using Lansky Index, NIHSS, NANO, GCS, and mRS. RESULTS: 21 pediatric and adolescent patients who underwent resection of CNS neoplasms were included. Of these, 8 (38.1%) were female with a mean (SD) age of 9.9 (5.2) years. During 13 (61.9%) resection an iAE was noted, of which 11 (52.4%) were classified as ClassIntra I and 2 (9.5%) as ClassIntra II. The majority (66.7%) underwent surgery for infratentorial pathology, whereas 4 (19.0%) had a supratentorial and 3 (14.3%) a spinal pathology. Preoperative characteristics did not correlate with the severity of ClassIntra. In patients without an iAE, a gross total resection was achieved more frequently (p=0.048). Focusing on postoperative outcome revealed a higher severity of cumulative complications as presented by the CCI (10.4 versus 40.5), longer hospital stay (p=0.04), and higher 30-day readmission rate (p

OBJECTIVE: The molecular classification of CNS tumors has revolutionized our understanding of the biological heterogeneity and diversity of tumor subtypes. DNA methylation-based classification allows to discriminate subtypes. Although DNA methylation-based classification can diagnose tumors with high specificity, there are tumors which cannot be classified. We aimed to gain further insight into these challenging cases. METHODS: Overall, 21 patients with a CNS tumor that was non-classifiable (confidence score

Purpose The Hippo pathway has broadened in cancer research in the past decade and revealed itself to be an important driver for tumorigenesis and metastatic spread. In this study, we investigated the clinical relevance of the Hippo pathway with regard to metastatic invasion, patients’ outcome and histopathological features. Methods Protein expression of components of the Hippo pathway were analyzed by immunohistochemistry (IHC) using paraffin-embedded tissue from 103 patients who had been diagnosed with pancreatic ductal adenocarcinoma and had undergone surgery. Results were correlated with clinicopathological data, disease-free and overall survival. Results Immunohistochemistry studies in pancreatic tumour tissues revealed a significant upregulation of MST1, MST2, pLATS, pYAP and 14-3-3, representing the active Hippo pathway, in non-metastasized patients (p p Conclusion The Hippo pathway is inactive in metastasized patients releasing the pro-metastatic and proliferative potential of the pathway. Furthermore, our study underlines the prognostic relevance of the Hippo pathway as a shift in the balance towards the inactive pathway predicts an unfavorable OS and DFS.

Background: The coronavirus disease 2019 (COVID-19) pandemic affects the education of medical students around the world and countries have had differing responses in dealing with this dynamic situation. The role of medical students in fighting this pandemic is controversial and it is yet to be elucidated how they can best be of service. The aim of this study is to evaluate the working fields of volunteering students and the impact of the pandemic on final year students from a student's perspective. Methods: An anonymous online survey was conducted amongst 219 medical students from Hamburg (Germany), using an institutional online data collection program. Results: A total of 137 questionnaires (63.5%) were completed. Of these, 97 participants were students from academic year three to five (70.8%) and 40 students were in the final year of medical school (29.2%). Of the 97 students from academic year three to five, 68 students (70.1%) signed up for voluntary duties during the pandemic. Interestingly, only 25.0% of the students were called for voluntary work in hospitals or health authorities. Final year students had already been working in hospitals since before the outbreak, with 35.0% of them assisting doctors in the treatment of COVID-19 positive patients during their placements. Using a 5-Point Likert Scale, the students who volunteered self-assessed their work as more useful and received more gratitude than final year students (p

Background Student-Run Free Clinics (SRFCs) have been an integral part of US medical schools since the 1960s and provide health care to underserved populations. In 2018, we established an SRFC in Hamburg, Germany, a major city in Northern Europe. The aim of this study was to describe the central problems and to investigate the usefulness of an SRFC in a country with free access to medical care, such as Germany. Methods All consecutive patients treated at the SRFC Hamburg between February 2018 and March 2019 that consented to this study were analyzed regarding clinical characteristics, diagnosis, readmission rate and country of origin. Results Between February 2018 and March 2019, 229 patients were treated at the SRFC in Hamburg. The patients came from 33 different countries with a majority (n = 206, 90%) from countries inside the European Union. The most common reasons for visiting the SRFC were infections (23.2%), acute or chronic wounds (13.5%) and fractures (6.3%). Conclusion Our multicultural patients suffer mainly from infections and traumatological and dermatological diseases. We find similarities to published Canadian SRFC patient cohorts but differences in diseases and treatment modalities compared to US SRFCs. Importantly, we demonstrate the relevance and necessity of the SRFC in a major city in Northern Europe.