77 research outputs found
Predictive Immunological Markers in Oncology
Most treatment decisions in oncology are still based on histomorphological criteria, criteria that are incorporated in actual staging systems. With just a few exceptions (i.e., leukemias, some lymphomas, GIST, NSCLC, etc.) molecular and immunological characteristics of individual tumors do not contribute to this process. The basis for clinical considerations and treatment indications are clinical trials. In these clinical trials, a specific treatment is associated with a statistical outcome for the entire patient population treated in this trial. Not surprisingly, a subgroup of patients does not benefit from the administered treatment an
Advanced Malignant Melanoma: Immunologic and Multimodal Therapeutic Strategies
Immunologic treatment strategies are established in malignant
melanoma treatment, mainly focusing on Interleukin-2 in advanced disease
and interferon alpha in the adjuvant situation. In advanced
disease, therapies with IL-2, interferon and different
chemotherapeutic agents were not associated with better patient
survival in the vast majority of patients. Therefore, an overview
of novel immunological agents and combined therapeutic approaches
is presented in this review, covering allogenic and autologous
vaccine strategies, dendritic cell vaccination, strategies for
adoptive immunotherapy and T cell receptor gene transfer,
treatment with cytokines and monoclonal antibodies against the
CTLA-4 antigen. As emerging treatment strategies are based on
individual molecular and immunological characterization of
individual tumors/patients, tailored targeted drug therapies move
into the focus of treatment strategies. Multimodal combination
therapies with considerable potential in altering the immune
response in malignant melanoma patients are currently emerging. As
oncology moves forward into the field of personalized therapies, a
careful molecular and immunological characterization of patients
is crucial to select patients for individual targeted treatment
Estimation of Immune Cell Densities in Immune Cell Conglomerates: An Approach for High-Throughput Quantification
Determining the correct number of positive immune cells in immunohistological sections of colorectal cancer and other tumor entities is emerging as an important clinical predictor and therapy selector for an individual patient. This task is usually obstructed by cell conglomerates of various sizes. We here show that at least in colorectal cancer the inclusion of immune cell conglomerates is indispensable for estimating reliable patient cell counts. Integrating virtual microscopy and image processing principally allows the high-throughput evaluation of complete tissue slides.For such large-scale systems we demonstrate a robust quantitative image processing algorithm for the reproducible quantification of cell conglomerates on CD3 positive T cells in colorectal cancer. While isolated cells (28 to 80 microm(2)) are counted directly, the number of cells contained in a conglomerate is estimated by dividing the area of the conglomerate in thin tissues sections (< or =6 microm) by the median area covered by an isolated T cell which we determined as 58 microm(2). We applied our algorithm to large numbers of CD3 positive T cell conglomerates and compared the results to cell counts obtained manually by two independent observers. While especially for high cell counts, the manual counting showed a deviation of up to 400 cells/mm(2) (41% variation), algorithm-determined T cell numbers generally lay in between the manually observed cell numbers but with perfect reproducibility.In summary, we recommend our approach as an objective and robust strategy for quantifying immune cell densities in immunohistological sections which can be directly implemented into automated full slide image processing systems
No Significant Bone Resorption after Open Treatment of Mandibular Condylar Head Fractures in the Medium-Term
Open treatment of condylar head fractures (CHF) is considered controversial. In this retrospective cohort study our primary objective was therefore to assess bone resorption and remodeling as well as patients function after open treatment of CHF in a medium-term follow-up (15.1 ± 2.2 months). We included 18 patients with 25 CHF who underwent open reduction and internal fixation, between 2016 and 2021, in our analysis. The clinical data and cone-beam computed tomography (CBCT) datasets were analyzed. The condylar processes were segmented in the postoperative (T1) and follow-up (T2) CBCT scans. Volumetric and linear bone changes were the primary outcome variables, measured by using a sophisticated 3D-algorithm. The mean condylar head volume decreased non-significantly from 3022.01 ± 825.77 mm3 (T1) to 2878.8 ± 735.60 mm3 (T2; p = 0.52). Morphological alterations indicated remodeling and resorption. The pre-operative maximal interincisal opening (MIO) was 19.75 ± 3.07 mm and significantly improved to 40.47 ± 1.7 mm during follow-up (p = 0.0005). Low rates of postoperative complications were observed. Open reduction of CHF leads to good clinical outcomes and low rates of medium-term complications. This study underlines the feasibility and importance of open treatment of CHF and may help to spread its acceptance as the preferred treatment option
Nimodipine vs. Milrinone – Equal or Complementary Use? A Retrospective Analysis
Background: Cerebral vasospasm (CVS) continues to account for high morbidity and
mortality in patients surviving the initial aneurysmal subarachnoid hemorrhage (SAH).
Nimodipine is the only drug known to reduce delayed cerebral ischemia (DCI), but it
is believed not to affect large vessel CVS. Milrinone has emerged as a promising option.
Our retrospective study focused on the effectiveness of the intra-arterial application of
both drugs in monotherapy and combined therapy.
Methods: We searched for patients with aneurysmal SAH, angiographically confirmed
CVS, and at least one intra-arterial pharmacological angioplasty. Ten defined vessel
sections on angiograms were assessed before and after vasodilator infusion. The
improvement in vessel diameters was compared to the frequency of DCI-related cerebral
infarction before hospital discharge and functional outcome reported as the modified
Rankin Scale (mRS) score after 6 months.
Results: Between 2014 and 2021, 132 intra-arterial interventions (144 vascular
territories, 12 bilaterally) in 30 patients were analyzed for this study. The vasodilating
effect of nimodipine was superior to milrinone in all intradural segments. There was
no significant intergroup difference concerning outcome in mRS (p = 0.217). Only
nimodipine or the combined approach could prevent DCI-related infarction (both 57.1%),
not milrinone alone (87.5%). Both drugs induced a doubled vasopressor demand due to
blood pressure decrease, but milrinone alone induced tachycardia.
Conclusions: The monotherapy with intra-arterial nimodipine was superior to milrinone.
Nimodipine and milrinone may be used complementary in an escalation scheme with the
administration of nimodipine first, complemented by milrinone in cases of severe CVS.
Milrinone monotherapy is not recommended
Is radical surgery of an inverted papilloma of the maxillary sinus obsolete? a case report
Abstract Background Sinonasal inverted papilloma is a locally aggressive tumor arising from the Schneiderian membrane which lines the nasal cavity and paranasal sinuses. Aggressive surgical approaches, such as lateral rhinotomy, were used until recently for complete removal of the inverted papilloma. Currently, endoscopic resection is the gold standard in the treatment of inverted papilloma. However, there are situations that justify an open approach. For example there are studies that report a higher postoperative recurrence rate after endonasal endoscopic resection, particularly in the treatment of recurrent diseases. While endoscopic resection performed by an experienced surgeon is definitely a minimally invasive therapy, an open approach is not necessarily associated with functional and aesthetic disadvantages. This case report describes the treatment of inverted papilloma by an open approach. This has been described before but the new gold standard of endoscopic resection has to be taken into account before any treatment decision is made nowadays. Case presentation Contrast-enhanced magnetic resonance imaging of the head and neck area was indicated in a 72-year-old white German man who presented with suspected squamous cell carcinoma of his lower lip. Magnetic resonance imaging additionally revealed a 3×2 cm2 polycyclic arranged mucosal thickening with cystic and solid contrast affine shares at the antral laterocaudal area of his right maxillary sinus, extending from his right lateral nasal wall to his maxillary sinus floor. He received antral polypectomy with medial maxillectomy via a unilateral LeFort I osteotomy approach. His pterygoid plate was preserved. A histological examination demonstrated a tumor composed of hyperplastic squamous epithelium protruding into the stroma (surface epithelial cells grew downward into the underlying supportive tissue), thus producing a grossly convoluted cerebriform appearance. Two weeks later, the patient regained a well-formed maxilla without any restrictions. He has remained disease-free for 25 months following the surgery and surveillance was continued in our tumor clinic. Conclusions Endoscopic resection of an inverted papilloma continues to be the gold standard. However, some cases require a radical approach. This does not necessarily increase patient morbidity
Immunotherapy of Colorectal Cancer
It is known that the immune response, reflected by high T cell infiltrates in primary tumors and metastases, influences the clinical course of colorectal cancer (CRC). Therefore, immunotherapy concepts have been adapted from other tumor entities, which typically rely on the activation of T cells in the tumor microenvironment (e.g. blockade of the immune checkpoint molecules PD-1 and CTLA-4). However, most of the strategies using the approved checkpoint inhibitors and/or combination strategies have more or less failed to produce impressive results in early phase trials in CRC. Therefore, a number of novel targets for checkpoint inhibition are currently in early phase clinical testing (TIM-3, Lag-3, OX40, GITR, 4-1BB, CD40, CD70). A simple activation of infiltrating T cells will not, however, lead to a meaningful anti-tumor response without modulating the environmental factors in CRC. Thus, it is absolutely necessary to improve our understanding of the complex regulation of the tumor microenvironment in CRC to design individual combination treatments leading to effective immune control
Standardized Diagnostic Workup and Patient-Centered Decision Making for Surgery and Neck Dissection Followed by Risk-Factor Adapted Adjuvant Therapy Improve Loco-Regional Control in Local Advanced Oral Squamous Cell Carcinoma
Background: Standardized staging procedures and presentation of oral squamous cell
carcinoma (OSCC) patients in multidisciplinary tumor boards (MDTB) before treatment
and utilization of elective neck dissection (ND) are expected to improve the outcome,
especially in local advanced LAOSCC (UICC stages III–IVB). As standardized diagnostics
but also increased heterogeneity in treatment applied so far have not been demonstrated
to improve outcome in LAOSCC, a retrospective study was initiated.
Methods: As MDTB was introduced into clinical routine in 2007, 316 LAOSCC patients
treated during 1991-2017 in our hospital were stratified into cohort 1 treated before
(n=104) and cohort 2 since 2007 (n=212). Clinical characteristics, diagnostic procedures
and treatment modality of patients were compared using Chi-square tests and outcome
analyzed applying Kaplan-Meier plots and log-rank tests as well as Cox proportional
hazard regression. Propensity scores (PS) were used to elucidate predictors for impaired
distant metastasis-free survival (DMFS) in PS-matched patients.
Results: Most patient characteristics and treatment modalities applied showed
insignificant alteration. Surgical treatment included significantly more often resection of
the primary tumor plus neck dissection, tracheostomy and percutaneous endoscopic
gastrostomy tube use. Cisplatin-based chemo-radiotherapy was the most frequent. Only
insignificant improved disease- (DFS), progression- (PFS) and event-free (EFS) as well as
tumor-specific (TSS) and overall survival (OS) were found after 2006 as local (LC) and locoregional
control (LRC) were significantly improved but DMFS significantly impaired.
Cox regression applied to PS-matched patients elucidated N3, belonging to cohort 2 and
cisplatin-based chemo-radiotherapy as independent predictors for shortened DMFS. The
along chemo-radiotherapy increased dexamethasone use in cohort 2 correlates with
increased DM.
Conclusions: Despite standardized diagnostic procedures, decision-making considering
clear indications and improved therapy algorithms leading to improved LC and LRC,
shortened DMFS hypothetically linked to increased dexamethasone use had a detrimental
effect on TSS and OS
In silico SNP analysis of the breast cancer antigen NY-BR-1
Background: Breast cancer is one of the most common malignancies with increasing incidences every year and a leading cause of death among women. Although early stage breast cancer can be effectively treated, there are limited numbers of treatment options available for patients with advanced and metastatic disease. The novel breast cancer associated antigen NY-BR-1 was identified by SEREX analysis and is expressed in the majority (>70%) of breast tumors as well as metastases, in normal breast tissue, in testis and occasionally in prostate tissue. The biological function and regulation of NY-BR-1 is up to date unknown. Methods: We performed an in silico analysis on the genetic variations of the NY-BR-1 gene using data available in public SNP databases and the tools SIFT, Polyphen and Provean to find possible functional SNPs. Additionally, we considered the allele frequency of the found damaging SNPs and also analyzed data from an in-house sequencing project of 55 breast cancer samples for recurring SNPs, recorded in dbSNP. Results: Over 2800 SNPs are recorded in the dbSNP and NHLBI ESP databases for the NY-BR-1 gene. Of these, 65 (2.07%) are synonymous SNPs, 191 (6.09%) are non-synoymous SNPs, and 2430 (77.48%) are noncoding intronic SNPs. As a result, 69 non-synoymous SNPs were predicted to be damaging by at least two, and 16 SNPs were predicted as damaging by all three of the used tools. The SNPs rs200639888, rs367841401 and rs377750885 were categorized as highly damaging by all three tools. Eight damaging SNPs are located in the ankyrin repeat domain (ANK), a domain known for its frequent involvement in protein-protein interactions. No distinctive features could be observed in the allele frequency of the analyzed SNPs. Conclusion: Considering these results we expect to gain more insights into the variations of the NY-BR-1 gene and their possible impact on giving rise to splice variants and therefore influence the function of NY-BR-1 in healthy tissue as well as in breast cancer
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