34 research outputs found
An integrated software approach to interactive exploration and steering of fluid flow simulations on many-core architectures
Traditionell werden numerische Strömungssimulationen in einer zyklischen Sequenz autonomer Teilschritte durchgeführt. Seitens Wissenschaftlern existiert jedoch schon lange der Wunsch nach mehr Interaktion mit laufenden Simulationen. Seit dem maßgeblichen Report der National Science Foundation im Jahre 1987 wurden daher neue Formen der wissenschaftlichen Visualisierung entwickelt, die sich grundlegend von den traditionellen Verfahren unterscheiden. Insbesondere hat der sogenannte Computational Steering-Ansatz reges Interesse bewirkt. Damals wie heute ist die Anwendung des Verfahrens jedoch eher die Ausnahme denn die Regel. Ursächlich dafür sind zu großen Teilen Komplexität und Restriktionen traditioneller Hochleistungssysteme. Im Rahmen dieser Arbeit wird daher als Alternative zu dem traditionellen Vorgehen die immense Leistungsfähigkeit moderner Grafikkartengenerationen für die Berechnungen herangezogen. Das sogenannte GPGPU-Computing eignet sich insbesondere für die Anwendung der Lattice-Boltzmann-Methode im Bereich numerischer Strömungssimulationen. Auf Grundlage des LBM-Verfahrens wird im Rahmen dieser Arbeit prototypisch eine interaktive Simulationsumgebung basierend auf dem Computational Steering-Paradigma entwickelt, das alle Prozesse zur Lösung von Strömungsproblemen innerhalb einer einzelnen Anwendung integriert. Durch die Konvergenz der hohen massiv parallelen Rechenleistung der GPUs und der Interaktionsfähigkeiten in einer einzelnen Anwendung kann eine erhebliche Steigerung der Anwendungsqualität erzielt werden. Dabei ist es durch Einsatz mehrerer GPUs möglich, dreidimensionale Strömungsprobleme mit praxisrelevanter Problemgröße zu berechnen und gleichzeitig eine interaktive Manipulation und Exploration des Strömungsgebiets zur Laufzeit zu ermöglichen. Dabei ist der erforderliche finanzielle Aufwand verglichen mit traditionellen massiv parallelen Verfahren verhältnismäßig gering.Traditionally, computational fluid dynamics is done in a cyclic sequence of independent steps. Howerver it is a long term wish of scientists and engineers to closely interact with their running simulations. Since the influential report of the US National Science Foundation in 1987 new forms of scientific visualization have evolved that are quite different from traditional post-processing. Especially the approach commonly referred to as computational steering has been the subject of widespread interest. Although it is a very powerful paradigm, the use of computational steering is still the exception rather than the rule. The reasons for this are more or less related to the complexity and restrictions of traditional HPC systems. As an alternative to the traditional massively parallel approach, in this thesis the parallel computational power of GPGPUs is used for general purpose applications. The so called GPGPU computing has gained large popularity in the CFD community, especially for its application to the lattice Boltzmann method. Using this technology this work demonstrates a single desktop application integrating a complete interactive CFD simulation environment for reasonable hardware costs. It shows that the convergence of massive parallel computational power and steering environment into a single system significantly improves the usability, application quality and user-friendliness. Using multiple GPUs, the efficiency of this approach allows for CFD simulations in three dimensional space evolving close to real-time even for reasonable grid sizes. Thereby, the simulation can be explored and also adjusted during runtime. The thesis also shows that the responsiveness significantly benefits from avoiding common bandwidth and latency bottlenecks inherent in traditional HPC approaches. Those can be avoided as GPGPU computing does not generally require network communication, which also reduces the complexity of the application
Multiple schwannomas of the facial nerve mimicking cervical lymphoma: a case report
Background
In this report, we describe the first case in literature of a patient with multiple schwannomas of the marginal mandibular branch of the facial nerve.
Case presentation
A Caucasian patient presented with a sudden onset of left lower facial nerve palsy House–Brackmann score III for 1 month. Computed tomography imaging was performed to exclude a cerebral event and revealed multiple tumors within the left parotid gland. Duplex ultrasound and magnetic resonance imaging scans delineated multiple, hypoechoic tumors, round in shape and well defined without a hilar structure along the left mandible. For histological verification, a left-side partial parotidectomy and extirpation of an intraparotideal node was performed with use of a nerve-integrity monitor. Histomorphological analysis of the resected tissue revealed a benign schwannoma. Facial nerve function remained unchanged since the operation. The size of the nonresected tumors is currently monitored regularly by ultrasonography. Fibromatosis has been excluded.
Conclusions
If multiple tumors occur in the parotid gland and the angle of the jaw, schwannomas need to be considered as a differential diagnosis. To plan the right diagnostic surgical intervention and prevent nerve damage, a thorough ultrasound examination is essential in preoperative diagnostic work-up for any suspicious lesion of the parotid gland and jaw region
Schwannoma of the Hypoglossal Nerve Mimicking Carotid Body Paraganglioma
Carotid body paragangliomas (CBPs) clinically present as highly vascularized cervical
masses with a pathognomonic localization at the carotid artery bifurcation. Following ultrasonography and MRI/CT imaging, surgical resection with optional preoperative embolization is considered
as the treatment of choice in most cases. We herein present the case of a 60-year-old female with
characteristic clinical signs and imaging findings of a right-sided CBP who finally went to surgical
treatment. Intraoperatively, the tumor showed an adherent growth to the hypoglossal nerve that
had to be partially resected, resulting in a postoperative nerve palsy. Histological examination of
the resected tumor revealed the unexpected diagnosis of a hypoglossal nerve schwannoma. To the
best of our knowledge, we herein present the third case reported in the literature of a unilateral
hypoglossal schwannoma located at the carotid bifurcation mimicking clinical symptoms, imaging
and intraoperative findings of a CBP
Differential nasal swab cytology represents a valuable tool for therapy monitoring but not prediction of therapy response in chronic rhinosinusitis with nasal polyps treated with Dupilumab
Introduction: Chronic Rhinosinusitis with nasal polyps (CRSwNP) is a common
chronic disease with a high impact on patients’ quality of life. If conservative and
surgical guideline treatment cannot sufficiently control disease burden,
biologicals can be considered as a comparably new treatment option that has
revolutionized CRSwNP therapy since the first approval of Dupilumab in 2019.
With the aim to select patients who benefit from this new treatment and to find a
marker for therapy monitoring, we investigated the cellular composition of nasal
mucous membranes and inflammatory cells of patients suffering from CRSwNP
and undergoing Dupilumab therapy using non-invasive nasal swab cytology.
Methods: Twenty CRSwNP patients with the indication for Dupilumab therapy
have been included in this prospective clinical study. In total, five study visits were
conducted with ambulatory nasal differential cytology using nasal swabs starting
with the beginning of therapy and followed by visits every 3 months for 12
months. First, these cytology samples were stained with the May-GrunwaldGiemsa method (MGG) and the percentage of ciliated cells, mucinous cells,
eosinophil cells, neutrophil cells, and lymphocytes was analyzed. Secondly, an
immunocytochemical (ICC) ECP-staining was performed to detect eosinophil
granulocytes. Additionally, during each study visit the nasal polyp score, SNOT20
questionnaire, olfactometry, the total IgE concentration in peripheral blood as
well as the eosinophil cell count in peripheral blood were recorded. The change
of parameters was evaluated over one year and the correlation between clinical
effectiveness and nasal differential cytology was analyzed.
Results: In both MGG (p<0.0001) and ICC analysis (p<0.001) a significant
decrease of eosinophils was seen under Dupilumab treatment. When patients
were divided into a Eo-low- (<21%) and Eo-high- (≥21%) group according to the
percentage eosinophils in nasal swab catology in the first study visit, the Eo-highgroup showed a greater change of eosinophils over time (D17.82) compared to
the Eo-low-group (D10.67) but, however, no better response to therapy. The
polyp score, SNOT20 questionnaire, and total IgE concentration in peripheral
blood showed a significant decrease during the observation period (p<0.0001).
Discussion: Nasal swab cytology as an easy-to-apply diagnostic method allows
detection and quantification of the different cell populations within the nasal
mucosa at a given time. The nasal differential cytology showed a significant
decrease of eosinophils during Dupilumab therapy and can therefore be used as
non-invasvive method for monitoring therapy success of this cost intensive
therapy and potentially can allow an optimized individual therapy planning and
management for CRSwNP patients. Since the validity of initial nasal swab
eosinophil cell count as a predictive biomarker for therapy response was
limited in our study, additional studies including larger number of participants
will be necessary to further evaluate the potential benefits for clinical practice of
this new diagnostic method
Complete remission of an early-stage laryngeal cancer under combined pembrolizumab and chemotherapy treatment of a synchronous lung adenocarcinoma
Background: Anti-PD1-Checkpoint inhibition (CI) is an established treatment of recurrent and/or metastatic head
and neck cancer. A potential beneft from CI in early-stage disease that is usually treated by radiation or surgery has
not been investigated so far and is currently not addressed in clinical trials.
Case presentation: A 58-year-old man was diagnosed with a cT2 supraglottic laryngeal cancer and a synchronous
metastasized adenocarcinoma of the lung. As the patient refused any treatment of his laryngeal cancer, he received
combined immune-chemotherapy according to the KEYNOTE-189 protocol. After 4 cycles of pembrolizumab/carboplatin/pemetrexed, the patient showed a complete remission of his laryngeal cancer with a clear shrinkage of
the mediastinal and hilar lung cancer metastases. After 21 cycles of maintenance therapy, the lung adenocarcinoma
shows a stable disease status with no signs of any residual or recurrent laryngeal cancer.
Conclusions: Anti-PD1-CI may be a treatment option also for early-stage HNSCC with excellent functional outcome
when established therapies are not available
Cytology-based Cancer Surgery of the Head and Neck (CyCaS-HN): a prospective, randomized, controlled clinical trial
Purpose Liquid-based cytology (LBC) is routinely used in gynecology but is rarely applied in head and neck oncology
though many suspicious lesions are easily accessible. While several studies have evaluated the potential use of LBC for early
detection and molecular characterization of head and neck squamous cell carcinomas (HNSCCs), no study investigated its
potential role in surgical management and therapy planning so far.
Methods Twenty-fve patients with cT1-2 squamous cell carcinomas of the oral cavity and oropharynx were prospectively
enrolled in this study and were randomized to two treatment arms: in the control arm, a diagnostic panendoscopy with incisional biopsy was followed by a second operation with transoral tumor resection±neck dissection and tracheostomy. In the
intervention arm, patients underwent LBC diagnostics and in case of a positive result received one single operation with
panendoscopy and incisional biopsy for confrmation of LBC result by rapid section histology followed by transoral tumor
resection±neck dissection and tracheostomy in the same session.
Results Time between clinical diagnosis and defnitive surgical treatment was signifcantly shorter in the intervention group
compared with the control group (p<0.0001). Additionally, time of hospitalization (p<0.0001) and cumulative operation
time (p=0.062) were shorter in the intervention group. No signifcant diferences in overall, progression-free, and diseasespecifc survival were observed.
Conclusion Cytology-based cancer surgery is a promising therapeutic strategy that can potentially be considered for a
well-defned group of early-stage HNSCC patients and help to avoid repetitive general anesthesia, shorten the diagnosis-totreatment interval and spare operation as well as hospitalization time
Expression of SEC62 Oncogene in Benign, Malignant and Borderline Melanocytic Tumors—Unmasking the Wolf in Sheep’s Clothing?
SEC62 oncogene located at chromosomal region 3q26 encodes for a transmembrane protein
of the endoplasmic reticulum (ER) and is expressed at high levels in numerous human malignancies. SEC62 overexpression has been associated with worse prognosis and high risk for lymphatic
and distant metastases in head and neck cancer, cervical cancer, hepatocellular cancer, and lung
cancer. However, its role in the development and tumor biology of melanocytic lesions has not
been investigated so far. An immunohistochemical study including 209 patients with melanocytic
lesions (malignant melanoma (MM), n = 93; melanoma metastases (MET), n = 28; Spitz nevi (SN),
n = 29; blue nevi (BN), n = 21; congenital nevi (CN), n = 38) was conducted and SEC62 expression
was correlated with clinical data including patient survival and histopathological characteristics.
SN showed the highest SEC62 expression levels followed by MET, MM, CN, and BN. High SEC62
expression correlated with a shorter overall and progression-free survival in MM patients. Additionally, high Sec62 levels correlated significantly with higher tumor size (T stage), the presence of
tumor ulceration, and the presence of lymph node as well as distant metastases. Strikingly, SEC62
expression showed a strong correlation with Clark level. Taken together, these data demonstrate that
SEC62 is a promising prognostic marker in MM and has the potential to predict biological behavior
and clinical aggressiveness of melanocytic lesions
Antagonizing Sec62 function in intracellular Ca2+ homeostasis represents a novel therapeutic strategy for head and neck cancer
Various cancer types including head and neck squamous cell carcinomas
(HNSCC) show a frequent amplification of chromosomal region 3q26 that
encodes, among others, for the SEC62 gene. Located in the ER membrane,
this translocation protein is known to play a critical role as a potential driver
oncogene in cancer development. High SEC62 expression levels were observed
in various cancer entities and were associated with a poor outcome and
increased metastatic burden. Because of its intracellular localization the
SEC62 protein is poorly accessible for therapeutic antibodies, therefore a
functional SEC62 knockdown represents the most promising mechanism of
a potential antineoplastic targeted therapy. By stimulating the Ca2+ efflux from
the ER lumen and thereby increasing cellular stress levels, a functional inhibition
of SEC62 bears the potential to limit tumor growth and metastasis formation. In
this study, two potential anti-metastatic and -proliferative agents that
counteract SEC62 function were investigated in functional in vitro assays by
utilizing an immortalized human hypopharyngeal cancer cell line as well as a
newly established orthotopic murine in vivo model. Additionally, a CRISPR/
Cas9 based SEC62 knockout HNSCC cell line was generated and functionally
characterized for its relevance in HNSCC cell proliferation and migration as well
as sensitivity to SEC62 targeted therapy in vitro
Expression of 3q Oncogene SEC62 Predicts Survival in Head and Neck Squamous Cell Carcinoma Patients Treated with Primary Chemoradiation
Primary chemoradiotherapy (CRT) is an established treatment option for locally advanced
head and neck squamous cell carcinomas (HNSCC) usually combining intensity modified radiotherapy with concurrent platinum-based chemotherapy. Though the majority of patients can be
cured with this regimen, treatment response is highly heterogeneous and can hardly be predicted.
SEC62 represents a metastasis stimulating oncogene that is frequently overexpressed in various
cancer entities and is associated with poor outcome. Its role in HNSCC patients undergoing CRT
has not been investigated so far. A total of 127 HNSCC patients treated with primary CRT were
included in this study. The median follow-up was 5.4 years. Pretherapeutic tissue samples of the
primary tumors were used for immunohistochemistry targeting SEC62. SEC62 expression, clinical
and histopathological parameters, as well as patient outcome, were correlated in univariate and
multivariate survival analyses. High SEC62 expression correlated with a significantly shorter overall
survival (p = 0.015) and advanced lymph node metastases (p = 0.024). Further significant predictors
of poor overall and progression-free survival included response to therapy (RECIST1.1), nodal status,
distant metastases, tobacco consumption, recurrence of disease, and UICC stage. In a multivariate
Cox hazard proportional regression analysis, only SEC62 expression (p = 0.046) and response to therapy (p < 0.0001) maintained statistical significance as independent predictors of the patients’ overall
survival. This study identified SEC62 as an independent prognostic biomarker in HNSCC patients
treated with primary CRT. The role of SEC62 as a potential therapeutic target and its interaction with
radiation-induced molecular alterations in head and neck cancer cells should further be investigated
Podoplanin expression in lymph node metastases of head and neck cancer and cancer of unknown primary patients
Introduction: Head and neck squamous cell carcinomas (HNSCCs) are cancers with generally poor prognosis.
Outcomes have not improved in decades, with more than half of the patients presenting with lymph node metastases
at the time of diagnosis. A unique subtype of HNSCC, cancer of unknown primary of the head and neck (HNCUP) is
associated with a poor outcome. Increased expression of the D2-40 gene (podoplanin) has been described for several
human malignancies and has been associated with increased metastatic potential of cancer cells.
Methods: In order to examine the role of podoplanin in lymph node metastasis of HNSCC generally and HNCUP specifically, we evaluated the prognostic impact of podoplanin expression in HNSCC- (n=68) and HNCUP-associated lymph
node metastases (n =30). The expression of podoplanin was analyzed by immunohistochemical staining of lymph node
tissue samples and correlated with clinical and histopathological data.
Results: We found a non-significant tendency towards a higher podoplanin expression in HNCUP compared to HNSCC
lymph node metastases and a significant correlation between a high podoplanin expression and advanced node-stage classification. Podoplanin expression had no significant impact on overall survival for both groups and did not correlate with
human papillomavirus tumor status.
Conclusion: Taken together, our results suggest that upregulation of podoplanin may be associated with a stimulation of
lymphatic metastasis in head and neck cancer