|
1
|
Bai X, Feng M, Ma W, Wang S. Predicting the efficacy of bevacizumab on peritumoral edema based on imaging features and machine learning. Sci Rep 2025; 15:15990. [PMID: 40341749 PMCID: PMC12062316 DOI: 10.1038/s41598-025-00758-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 04/30/2025] [Indexed: 05/11/2025] Open
Abstract
This study proposes a novel approach to predict the efficacy of bevacizumab (BEV) in treating peritumoral edema in metastatic brain tumor patients by integrating advanced machine learning (ML) techniques with comprehensive imaging and clinical data. A retrospective analysis was performed on 300 patients who received BEV treatment from September 2013 to January 2024. The dataset incorporated 13 predictive features: 8 clinical variables and 5 radiological variables. The dataset was divided into a training set (70%) and a test set (30%) using stratified sampling. Data preprocessing was carried out through methods such as handling missing values with the MICE method, detecting and adjusting outliers, and feature scaling. Four algorithms, namely Random Forest (RF), Logistic Regression, Gradient Boosting Tree, and Naive Bayes, were selected to construct binary classification models. A tenfold cross-validation strategy was implemented during training, and techniques like regularization, hyperparameter optimization, and oversampling were used to mitigate overfitting. The RF model demonstrated superior performance, achieving an accuracy of 0.89, a precision of 0.94, F1-score of 0.92, with both AUC-ROC and AUC-PR values reaching 0.91. Feature importance analysis consistently identified edema volume as the most significant predictor, followed by edema index, patient age, and tumor volume. Traditional multivariate logistic regression corroborated these findings, confirming that edema volume and edema index were independent predictors (p < 0.01). Our results highlight the potential of ML-driven predictive models in optimizing BEV treatment selection, reducing unnecessary treatment risks, and improving clinical decision-making in neuro-oncology.
Collapse
Affiliation(s)
- Xuexue Bai
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China
| | - Ming Feng
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China.
| | - Wenbin Ma
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China.
| | - Shiyong Wang
- Neurosurgery of The First Affiliated Hospital, Jinan University, Guangzhou, China.
| |
Collapse
|
|
2
|
Hatiboglu MA, Karacam B, Khan I, Akdur K, Elbasan EB, Mahfooz S, Seyithanoglu MH, Cetin G, Papaker MG, Oztanir MN. Liquid biopsy for CNS lymphoma: CSF exosomes and CSF exosomal miR-15a, miR-21, miR-155, miR-210, and miR-19b are promising biomarkers for diagnosis. Mol Biol Rep 2024; 51:1035. [PMID: 39361107 DOI: 10.1007/s11033-024-09967-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 09/23/2024] [Indexed: 10/05/2024]
Abstract
BACKGROUND Central nervous system lymphoma (CNSL) is a devastating disease with a poor prognosis. Early diagnosis, monitoring of the treatment response, and outcome prediction carry the utmost importance in the management of patients with CNSL. Surgical biopsy is the gold standard for tissue diagnosis, however, this procedure has potential complications. Therefore, there is a need for a method that provides information about diagnosis and patient monitoring to avoid surgical risks. The study aimed to investigate potential diagnostic biomarkers for patients with CNSL. METHODS AND RESULTS Patients with secondary CNSL were included in this study. Serum and cerebrospinal fluid (CSF) samples were collected before treatment and after completion of the treatment. Cell-free DNA (cfDNA), exosomes, free and exosomal microRNA (miR)-15a, miR-21, miR-155, miR-210, and miR-19b in both serum and CSF were examined, and they were compared with the controls. Also, their levels before and after treatment were compared. Nine patients with the diagnosis of secondary CNSL were reviewed. cfDNA, miR-15a, and miR-155 in serum, and exosome in CSF were found to be significantly higher in CNSL patients compared to the controls. Exosomal miR-15a, miR-21, miR-155, miR-210, and miR-19b in CSF were found to be significantly higher in CNSL patients compared to controls, whereas their levels in serum were not significantly high. CONCLUSIONS Our findings suggested that exosomes and exosomal miR-15a, miR-21, miR-155, miR-210 and miR-19b in CSF would be promising biomarkers for the diagnosis of patients with CNSL. Further studies are needed to confirm our findings.
Collapse
Affiliation(s)
- Mustafa Aziz Hatiboglu
- Department of Neurosurgery, Bezmialem Vakif University Medical School, Vatan Street, Fatih, Istanbul, Turkey.
- Department of Molecular Biology, Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Yalikoy, Beykoz, Istanbul, Turkey.
| | - Busra Karacam
- Department of Molecular Biology, Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Yalikoy, Beykoz, Istanbul, Turkey
| | - Imran Khan
- Department of Molecular Biology, Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Yalikoy, Beykoz, Istanbul, Turkey
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Kerime Akdur
- Department of Neurosurgery, Bezmialem Vakif University Medical School, Vatan Street, Fatih, Istanbul, Turkey
| | - Elif Burce Elbasan
- Department of Molecular Biology, Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Yalikoy, Beykoz, Istanbul, Turkey
| | - Sadaf Mahfooz
- Department of Molecular Biology, Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Yalikoy, Beykoz, Istanbul, Turkey
| | - Mehmet Hakan Seyithanoglu
- Department of Neurosurgery, Bezmialem Vakif University Medical School, Vatan Street, Fatih, Istanbul, Turkey
| | - Guven Cetin
- Department of Hematology, Bezmialem Vakif University Medical School, Vatan Street, Fatih, Istanbul, Turkey
| | - Meliha Gundag Papaker
- Department of Neurosurgery, Bezmialem Vakif University Medical School, Vatan Street, Fatih, Istanbul, Turkey
| | - Mustafa Namik Oztanir
- Department of Neurosurgery, Bezmialem Vakif University Medical School, Vatan Street, Fatih, Istanbul, Turkey
| |
Collapse
|
|
3
|
Hasner MC, van Opijnen MP, van der Meulen M, Verdijk RM, Maas SLN, Te Boome LCJ, Broekman MLD. Diagnostics and treatment delay in primary central nervous system lymphoma: What the neurosurgeon should know. Acta Neurochir (Wien) 2024; 166:261. [PMID: 38858236 PMCID: PMC11164806 DOI: 10.1007/s00701-024-06138-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 05/19/2024] [Indexed: 06/12/2024]
Abstract
PURPOSE The gold standard for diagnostics in primary central nervous system lymphoma (PCNSL) is histopathological diagnosis after stereotactic biopsy. Yet, PCNSL has a multidisciplinary diagnostic work up, which associated with diagnostic delay and could result in treatment delay. This article offers recommendations to neurosurgeons involved in clinical decision-making regarding (novel) diagnostics and care for patients with PCNSL with the aim to improve uniformity and timeliness of the diagnostic process for patients with PCNSL. METHODS We present a mini review to discuss the role of stereotactic biopsy in the context of novel developments in diagnostics for PCNSL, as well as the role for cytoreductive surgery. RESULTS Cerebrospinal fluid-based diagnostics are supplementary and cannot replace stereotactic biopsy-based diagnostics. CONCLUSION Histopathological diagnosis after stereotactic biopsy of the brain remains the gold standard for diagnosis. Additional diagnostics should not be a cause of diagnostic delay. There is currently no sufficient evidence supporting cytoreductive surgery in PCNSL, with recent studies showing contradictive data and suboptimal study designs.
Collapse
Affiliation(s)
- M C Hasner
- Department of Neurosurgery, Haaglanden Medical Centre, The Hague, The Netherlands.
| | - M P van Opijnen
- Department of Neurosurgery, Leiden University Medical Centre, Leiden, The Netherlands
| | - M van der Meulen
- Department of Neurology, Medisch Spectrum Twente, Enschede, The Netherlands
| | - R M Verdijk
- Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands
- Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - S L N Maas
- Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands
- Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - L C J Te Boome
- Department of Hematology, Haaglanden Medical Centre, The Hague, The Netherlands
| | - M L D Broekman
- Department of Neurosurgery, Haaglanden Medical Centre, The Hague, The Netherlands
- Department of Neurosurgery, Leiden University Medical Centre, Leiden, The Netherlands
| |
Collapse
|
|
4
|
Namale PE, Boloko L, Vermeulen M, Haigh KA, Bagula F, Maseko A, Sossen B, Lee-Jones S, Msomi Y, McIlleron H, Mnguni AT, Crede T, Szymanski P, Naude J, Ebrahim S, Vallie Y, Moosa MS, Bandeker I, Hoosain S, Nicol MP, Samodien N, Centner C, Dowling W, Denti P, Gumedze F, Little F, Parker A, Price B, Schietekat D, Simmons B, Hill A, Wilkinson RJ, Oliphant I, Hlungulu S, Apolisi I, Toleni M, Asare Z, Mpalali MK, Boshoff E, Prinsloo D, Lakay F, Bekiswa A, Jackson A, Barnes A, Johnson R, Wasserman S, Maartens G, Barr D, Schutz C, Meintjes G. Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial. Trials 2024; 25:311. [PMID: 38720383 PMCID: PMC11077808 DOI: 10.1186/s13063-024-08119-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 04/16/2024] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB. METHODS This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events. DISCUSSION Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice. TRIAL REGISTRATION ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986.
Collapse
Affiliation(s)
- Phiona E Namale
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
- Department of Medicine, University of Cape Town, Cape Town, South Africa.
| | - Linda Boloko
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Marcia Vermeulen
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Kate A Haigh
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
| | - Fortuna Bagula
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Alexis Maseko
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Bianca Sossen
- Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Scott Lee-Jones
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Yoliswa Msomi
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Helen McIlleron
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Ayanda Trevor Mnguni
- Department of Medicine, Khayelitsha Hospital, Cape Town, South Africa
- Department of Medicine, Stellenbosch University, Stellenbosch, South Africa
| | - Thomas Crede
- Department of Medicine, University of Cape Town, Cape Town, South Africa
- Department of Medicine, Mitchells Plain Hospital, Cape Town, South Africa
| | - Patryk Szymanski
- Department of Medicine, University of Cape Town, Cape Town, South Africa
- Department of Medicine, Mitchells Plain Hospital, Cape Town, South Africa
| | - Jonathan Naude
- Department of Medicine, University of Cape Town, Cape Town, South Africa
- Department of Medicine, Mitchells Plain Hospital, Cape Town, South Africa
| | - Sakeena Ebrahim
- Department of Medicine, University of Cape Town, Cape Town, South Africa
- Department of Medicine, Mitchells Plain Hospital, Cape Town, South Africa
| | - Yakoob Vallie
- Department of Medicine, New Somerset Hospital, Cape Town, South Africa
| | | | - Ismail Bandeker
- Department of Medicine, New Somerset Hospital, Cape Town, South Africa
| | - Shakeel Hoosain
- Department of Medicine, New Somerset Hospital, Cape Town, South Africa
| | - Mark P Nicol
- Division of Medical Microbiology, Department of Pathology, University of Cape Town, Cape Town, South Africa
- Division of Infection and Immunity School of Biomedical Sciences, University of Western Australia, Perth, Australia
| | - Nazlee Samodien
- Division of Medical Microbiology, Department of Pathology, University of Cape Town, Cape Town, South Africa
| | - Chad Centner
- Division of Medical Microbiology, Department of Pathology, University of Cape Town, Cape Town, South Africa
| | - Wentzel Dowling
- Division of Medical Microbiology, Department of Pathology, University of Cape Town, Cape Town, South Africa
| | - Paolo Denti
- Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Freedom Gumedze
- Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa
| | - Francesca Little
- Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa
| | - Arifa Parker
- Department of Medicine, Stellenbosch University, Stellenbosch, South Africa
| | - Brendon Price
- Division of Anatomical Pathology, Department of Pathology, University of Cape Town, Cape Town, South Africa
| | - Denzil Schietekat
- Department of Medicine, Khayelitsha Hospital, Cape Town, South Africa
- Department of Medicine, Stellenbosch University, Stellenbosch, South Africa
| | - Bryony Simmons
- LSE Health, London School of Economics and Political Science, London, UK
| | - Andrew Hill
- LSE Health, London School of Economics and Political Science, London, UK
| | - Robert J Wilkinson
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Department of Medicine, University of Cape Town, Cape Town, South Africa
- Francis Crick Institute, London, UK
- Department of Medicine, Imperial College London, London, UK
| | - Ida Oliphant
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Siphokazi Hlungulu
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Ivy Apolisi
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Monica Toleni
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Zimkhitha Asare
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Mkanyiseli Kenneth Mpalali
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Erica Boshoff
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Denise Prinsloo
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Francisco Lakay
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Abulele Bekiswa
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Amanda Jackson
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Ashleigh Barnes
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Ryan Johnson
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Sean Wasserman
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Gary Maartens
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - David Barr
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Charlotte Schutz
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Graeme Meintjes
- Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Department of Medicine, University of Cape Town, Cape Town, South Africa
| |
Collapse
|
|
5
|
Nunez JJ, Leung B, Ho C, Ng RT, Bates AT. Predicting which patients with cancer will see a psychiatrist or counsellor from their initial oncology consultation document using natural language processing. COMMUNICATIONS MEDICINE 2024; 4:69. [PMID: 38589545 PMCID: PMC11001970 DOI: 10.1038/s43856-024-00495-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Accepted: 03/28/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND Patients with cancer often have unmet psychosocial needs. Early detection of who requires referral to a counsellor or psychiatrist may improve their care. This work used natural language processing to predict which patients will see a counsellor or psychiatrist from a patient's initial oncology consultation document. We believe this is the first use of artificial intelligence to predict psychiatric outcomes from non-psychiatric medical documents. METHODS This retrospective prognostic study used data from 47,625 patients at BC Cancer. We analyzed initial oncology consultation documents using traditional and neural language models to predict whether patients would see a counsellor or psychiatrist in the 12 months following their initial oncology consultation. RESULTS Here, we show our best models achieved a balanced accuracy (receiver-operating-characteristic area-under-curve) of 73.1% (0.824) for predicting seeing a psychiatrist, and 71.0% (0.784) for seeing a counsellor. Different words and phrases are important for predicting each outcome. CONCLUSION These results suggest natural language processing can be used to predict psychosocial needs of patients with cancer from their initial oncology consultation document. Future research could extend this work to predict the psychosocial needs of medical patients in other settings.
Collapse
Affiliation(s)
- John-Jose Nunez
- BC Cancer, Vancouver, BC, Canada.
- Department of Computer Science, University of British Columbia, Vancouver, BC, Canada.
- Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
| | | | | | - Raymond T Ng
- Department of Computer Science, University of British Columbia, Vancouver, BC, Canada
| | - Alan T Bates
- BC Cancer, Vancouver, BC, Canada
- Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| |
Collapse
|
|
6
|
Huang L, Sun Q, Li Q, Li X. Screening and characterization of an anti-inflammatory pectic polysaccharide from Cucurbita moschata Duch. Int J Biol Macromol 2024; 264:130510. [PMID: 38447847 DOI: 10.1016/j.ijbiomac.2024.130510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Revised: 01/15/2024] [Accepted: 02/26/2024] [Indexed: 03/08/2024]
Abstract
Pectin polysaccharides have demonstrated diverse biological activities, however, the inflammatory potential of pectin polysaccharides extracted from Cucurbita moschata Duch remains unexplored. This study aims to extract, characterize and evaluate the effects of pumpkin pectin polysaccharide on lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 cells and dextran sulfate sodium (DSS)-induced colitis in mice, along with its underlying mechanism of action. Initially, we extracted three fractions of pectin polysaccharides from pumpkin and screened them for anti-inflammatory activity in LPS-induced macrophages, identifying CMDP-3a as the most potent anti-inflammatory fraction. Subsequently, CMDP-3a underwent comprehensive characterization through chromatography and spectroscopic analysis, revealing CMDP-3a as an RG-I-HG type pectin polysaccharide with →4)-α-D-GalpA-(1 → and →4)-α-D-GalpA-(1 → 2,4)-α-L-Rhap-(1 → as the main chain. Further, in the LPS-induced RAW264.7 cells model, treatment with CMDP-3a significantly down-regulated the mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) by inhibiting the MAPK and NF-κB signaling pathways. Finally, in a mouse colitis model, CMDP-3a administration obviously inhibited DSS-induced pathological alterations and reduced inflammatory cytokine expressions in the colonic tissues by down-regulating the TLR4/NF-κB and MAPK pathways. These findings provide a molecular basis for the potential application of CMDP-3a in reducing inflammatory responses.
Collapse
Affiliation(s)
- Linlin Huang
- The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan 250014, PR China
| | - Qi Sun
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China
| | - Quanhong Li
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China
| | - Xin Li
- The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan 250014, PR China; School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, PR China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China.
| |
Collapse
|
|
7
|
Stadler C, Gramatzki D, Le Rhun E, Hottinger AF, Hundsberger T, Roelcke U, Läubli H, Hofer S, Seystahl K, Wirsching HG, Weller M, Roth P. Glioblastoma in the oldest old: Clinical characteristics, therapy, and outcome in patients aged 80 years and older. Neurooncol Pract 2024; 11:132-141. [PMID: 38496908 PMCID: PMC10940826 DOI: 10.1093/nop/npad070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2024] Open
Abstract
Background Incidence rates of glioblastoma in very old patients are rising. The standard of care for this cohort is only partially defined and survival remains poor. The aims of this study were to reveal current practice of tumor-specific therapy and supportive care, and to identify predictors for survival in this cohort. Methods Patients aged 80 years or older at the time of glioblastoma diagnosis were retrospectively identified in 6 clinical centers in Switzerland and France. Demographics, clinical parameters, and survival outcomes were annotated from patient charts. Cox proportional hazards modeling was performed to identify parameters associated with survival. Results Of 107 patients, 45 were diagnosed by biopsy, 30 underwent subtotal resection, and 25 had gross total resection. In 7 patients, the extent of resection was not specified. Postoperatively, 34 patients did not receive further tumor-specific treatment. Twelve patients received radiotherapy with concomitant temozolomide, but only 2 patients had maintenance temozolomide therapy. Fourteen patients received temozolomide alone, 35 patients received radiotherapy alone, 1 patient received bevacizumab, and 1 took part in a clinical trial. Median progression-free survival (PFS) was 3.3 months and median overall survival (OS) was 4.2 months. Among patients who received any postoperative treatment, median PFS was 3.9 months and median OS was 7.2 months. Karnofsky performance status (KPS) ≥70%, gross total resection, and combination therapy were associated with better outcomes. The median time spent hospitalized was 30 days, accounting for 23% of the median OS. End-of-life care was mostly provided by nursing homes (n = 20; 32%) and palliative care wards (n = 16; 26%). Conclusions In this cohort of very old patients diagnosed with glioblastoma, a large proportion was treated with best supportive care. Treatment beyond surgery and, in particular, combined modality treatment were associated with longer OS and may be considered for selected patients even at higher ages.
Collapse
Affiliation(s)
- Christina Stadler
- Department of Neurology and Brain Tumor Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Dorothee Gramatzki
- Department of Neurology and Brain Tumor Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Emilie Le Rhun
- Department of Neurology and Brain Tumor Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Zurich
- Inserm, University of Lille, Lille, France
- Neuro-Oncology, General and Stereotaxic Neurosurgery Service, University Hospital of Lille, Lille, France
| | - Andreas F Hottinger
- Departments of Oncology & Clinical Neurosciences, Lundin Family Brain Tumor Research Center, Lausanne University Hospital & University of Lausanne, Lausanne, Switzerland
| | - Thomas Hundsberger
- Department of Neurology and Department of Medical Oncology and Haematology, Cantonal Hospital, St. Gallen, Switzerland
| | | | - Heinz Läubli
- Division of Oncology, University Hospital Basel, Basel, Switzerland
- Department of Biomedicine, University of Basel, Basel, Switzerland
| | - Silvia Hofer
- Department of Neurology and Brain Tumor Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Katharina Seystahl
- Department of Neurology and Brain Tumor Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Hans-Georg Wirsching
- Department of Neurology and Brain Tumor Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Michael Weller
- Department of Neurology and Brain Tumor Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Patrick Roth
- Department of Neurology and Brain Tumor Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| |
Collapse
|
|
8
|
Tang Y, Zhou M, Mao Z, Zhu B, Zhou F, Ye X, Chen Y, Ding Z. Structure of a polysaccharide MDP2-1 from Melastoma dodecandrum Lour. and its anti-inflammatory effects. Int J Biol Macromol 2024; 265:131015. [PMID: 38521298 DOI: 10.1016/j.ijbiomac.2024.131015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Revised: 03/01/2024] [Accepted: 03/18/2024] [Indexed: 03/25/2024]
Abstract
The anti-inflammatory activity of polysaccharides derived from Melastoma dodecandrum Lour. was evaluated in pyretic mice and HEK-Blue™ hTLR4 cells. The testing led to the identification of MDP2-1, which was then investigated for its structural characteristics and anti-inflammatory effects. Results showed that MDP2-1 had a molecular weight of 29.234 kDa and primarily consisted of galactose, arabinose, rhamnose, glucose, glucuronic acid, and galacturonic acid. Its main backbone was composed of →4)-α-D-GalpA-(1→, →2)-α-L-Rhap-(1→, →3,4)-α-D-GalpA-(1→, →2,4)-α-D-GlcpA-(1→, and its side chains were connected by →4)-α-D-Galp-(1→, α-D-Galp-(1→, →4)-β-D-Glcp-(1→, and α-L-Araf-(1→. In vivo experiments on mice demonstrated that MDP2-1 attenuated LPS-induced acute lung injury, and in vitro experiments on RAW264.7 cells showed that MDP2-1 reduced the levels of inflammatory mediators and mitigated LPS-induced inflammatory damage by inhibiting the activation of the TLR4 downstream NF-κB/MAPK pathway. These findings suggest that MDP2-1 is a novel anti-inflammatory agent for therapeutic interventions.
Collapse
Affiliation(s)
- Youying Tang
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China
| | - Mingyuan Zhou
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China
| | - Zian Mao
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China
| | - Bingqi Zhu
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China
| | - Fangmei Zhou
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China
| | - Xiaoqing Ye
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China
| | - Yuchi Chen
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.
| | - Zhishan Ding
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.
| |
Collapse
|
|
9
|
Kurdi M, Fadul MM, Addas BMJ, Faizo E, Alkhayyat S, Bamaga AK, Alsinani T, Katib Y, Okal F, Maghrabi Y, Sabbagh AJ, Moshref R, Albalawi S, Alkhotani A, Halawa TF, Mulla N, Hakamy S, Baeesa S. Dynamic interplay between corticosteroid treatment and the role of SRC-1 gene dysregulation in the progression of WHO-Grade 4 Astrocytoma. J Neurooncol 2023; 163:693-705. [PMID: 37402091 PMCID: PMC10393858 DOI: 10.1007/s11060-023-04385-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 06/26/2023] [Indexed: 07/05/2023]
Abstract
BACKGROUND Corticosteroid is commonly used before surgery to control cerebral oedema in brain tumours and is frequently continued throughout treatment. Its long-term effect of on the recurrence of WHO-Grade 4 astrocytoma remains controversial. The interaction between corticosteroid, SRC-1 gene and cytotoxic T-cells has never been investigated. METHODS A retrospective cohort of 36 patients with WHO-Grade 4 astrocytoma were examined for CD8 + T-cell and SRC-1 gene expressions through IHC and qRT-PCR. The impact of corticosteroid on CD8+T-cells infiltration, SRC-1 expression, and tumour recurrence was analyzed. RESULTS The mean patients age was 47-years, with a male to female ratio 1.2. About 78% [n = 28] of the cases showed reduced or no CD8+T-cell expression while 22% [n = 8] of cases have showed medium to high CD8+T-cell expression. SRC-1 gene was upregulated in 5 cases [14%] and 31 cases [86%] showed SRC-1 downregulation. The average of total days and doses of administered corticosteroid from the preoperative period to the postoperative period was at range of 14-106 days and 41-5028 mg, respectively. There was no significant statistical difference in RFI among tumours expressing high or low CD8+T-cells when corticosteroid was administered in recommended or exceeded doses [p-value = 0.640]. There was a significant statistical difference in RFI between CD8+T-Cell expression and SRC-1 gene dysregulation [p-value = 002]. Tumours with high CD8+T T-cell expression and SRC-1 gene downregulation had late recurrence. CONCLUSIONS Corticosteroid treatment can directly affect the SRC-1 gene regulation but does not directly influence cytotoxic T-cells infiltration or tumor progression. However, SRC-1 gene downregulation can facilitate late tumor recurrence.
Collapse
Affiliation(s)
- Maher Kurdi
- Department of Pathology, Faculty of Medicine, King Abdulaziz University, Rabigh, Kingdom of Saudi Arabia.
- Neuromuscular Unit, King Fahad Medical Research Center, Jeddah, Saudi Arabia.
| | - Motaz M Fadul
- Department of Pathology, Faculty of Medicine, King Abdulaziz University, Rabigh, Kingdom of Saudi Arabia
| | - Bassam M J Addas
- Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Eyad Faizo
- Department of Surgery, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia
| | - Shadi Alkhayyat
- Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University and Hospital, Jeddah, Saudi Arabia
| | - Ahmed K Bamaga
- Department of Paediatric, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Taghreed Alsinani
- Department of Neurosurgery, King Fahad General Hospital, Jeddah, Saudi Arabia
| | - Yousef Katib
- Department of Radiology, Faculty of Medicine, Taibah University, Madinah, Saudi Arabia
| | - Fahad Okal
- Department of Neuroscience, Neurosurgery Section, King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, Saudi Arabia
| | - Yazid Maghrabi
- Department of Neuroscience, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
| | - Abdulrahman J Sabbagh
- Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Rana Moshref
- Department of Neuroscience, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
| | - Sultan Albalawi
- Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Alaa Alkhotani
- Department of Pathology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Taher F Halawa
- Department of Paediatric, Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia
| | - Nasser Mulla
- Department of Internal Medicine, Faculty of Medicine, Taibah University, Medina, Saudi Arabia
| | - Sahar Hakamy
- Neuromuscular Unit, King Fahad Medical Research Center, Jeddah, Saudi Arabia
| | - Saleh Baeesa
- Department of Neuroscience, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
| |
Collapse
|
|
10
|
He J, He S, Zhang Y, Tian Y, Hao P, Li T, Xiao Y, Peng L, Feng Y, Cheng X, Deng H, Wang P, Chong W, Hai Y, Chen L, You C, Jia L, Chen D, Fang F. Association between intraoperative steroid and postoperative mortality in patients undergoing craniotomy for brain tumor. Front Neurol 2023; 14:1153392. [PMID: 37456646 PMCID: PMC10339830 DOI: 10.3389/fneur.2023.1153392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Accepted: 06/12/2023] [Indexed: 07/18/2023] Open
Abstract
Background Despite the widespread use of intraoperative steroids in various neurological surgeries to reduce cerebral edema and other adverse symptoms, there is sparse evidence in the literature for the optimal and safe usage of intraoperative steroid administration in patients undergoing craniotomy for brain tumors. We aimed to investigate the effects of intraoperative steroid administration on postoperative 30-day mortality in patients undergoing craniotomy for brain tumors. Methods Adult patients who underwent craniotomy for brain tumors between January 2011 to January 2020 were included at West China Hospital, Sichuan University in this retrospective cohort study. Stratified analysis based on the type of brain tumor was conducted to explore the potential interaction. Results This study included 8,663 patients undergoing craniotomy for brain tumors. In patients with benign brain tumors, intraoperative administration of steroids was associated with a higher risk of postoperative 30-day mortality (adjusted OR 1.98, 95% CI 1.09-3.57). However, in patients with malignant brain tumors, no significant association was found between intraoperative steroid administration and postoperative 30-day mortality (adjusted OR 0.86, 95% CI 0.55-1.35). Additionally, administration of intraoperative steroids was not associated with acute kidney injury (adjusted OR 1.11, 95% CI 0.71-1.73), pneumonia (adjusted OR 0.89, 95% CI 0.74-1.07), surgical site infection (adjusted OR 0.78, 95% CI 0.50-1.22) within 30 days, and stress hyperglycemia (adjusted OR 1.05, 95% CI 0.81-1.38) within 24 h after craniotomy for brain tumor. Conclusion In patients undergoing craniotomy for benign brain tumors, intraoperative steroids were associated with 30-day mortality, but this association was not significant in patients with malignant brain tumors.
Collapse
Affiliation(s)
- Jialing He
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Shuanghong He
- Health Management Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yu Zhang
- Evidence-Based Medicine Center, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
| | - Yixin Tian
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Pengfei Hao
- Department of Neurosurgery, Shanxi Provincial People’s Hospital, Taiyuan, Shanxi, China
| | - Tiangui Li
- Department of Neurosurgery, Longquan Hospital, Chengdu, Sichuan, China
| | - Yangchun Xiao
- Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
| | - Liyuan Peng
- Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
| | - Yuning Feng
- Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
| | - Xin Cheng
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Haidong Deng
- Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
| | - Peng Wang
- Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
| | - Weelic Chong
- Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA, United States
| | - Yang Hai
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States
| | - Lvlin Chen
- Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
| | - Chao You
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lu Jia
- Department of Neurosurgery, Shanxi Provincial People’s Hospital, Taiyuan, Shanxi, China
| | - Dengkui Chen
- Department of Neurosurgery, Sichuan Friendship Hospital, Chengdu, Sichuan, China
| | - Fang Fang
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| |
Collapse
|
|
11
|
Chen G, Jiang N, Zheng J, Hu H, Yang H, Lin A, Hu B, Liu H. Structural characterization and anti-inflammatory activity of polysaccharides from Astragalus membranaceus. Int J Biol Macromol 2023; 241:124386. [PMID: 37054858 DOI: 10.1016/j.ijbiomac.2023.124386] [Citation(s) in RCA: 63] [Impact Index Per Article: 31.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 03/18/2023] [Accepted: 04/05/2023] [Indexed: 04/15/2023]
Abstract
In this study, two homogeneous polysaccharides (APS-A1 and APS-B1) were isolated from Astragalus membranaceus by DEAE-52 cellulose and Sephadex G-100 column chromatography. Their chemical structures were characterized by molecular weight distribution, monosaccharide composition, infrared spectrum, methylation analysis, and NMR. The results revealed that APS-A1 (2.62 × 106 Da) was a 1,4-α-D-Glcp backbone with a 1,4,6-α-D-Glcp branch every ten residues. APS-B1 (4.95 × 106 Da) was a heteropolysaccharide composed of glucose, galactose, and arabinose (75.24:17.27:19.35). Its backbone consisted of 1,4-α-D-Glcp, 1,4,6-α-D-Glcp, 1,5-α-L-Araf and the sidechains composed of 1,6-α-D-Galp and T-α/β-Glcp. Bioactivity assays showed that APS-A1 and APS-B1 had potential anti-inflammatory activity. They could inhibit the production of inflammatory factors (TNF-α, IL-6, and MCP-1) in LPS-stimulated RAW264.7 macrophages via NF-κB and MAPK (ERK, JNK) pathways. These results suggested that the two polysaccharides could be potential anti-inflammatory supplements.
Collapse
Affiliation(s)
- Guangming Chen
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China
| | - Nan Jiang
- Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430061, PR China; Hubei Province Academy of Traditional Chinese Medicine, Wuhan 430074, PR China
| | - Junping Zheng
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China
| | - Haiming Hu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China
| | - Huabing Yang
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China
| | - Aizhen Lin
- Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430061, PR China; Hubei Province Academy of Traditional Chinese Medicine, Wuhan 430074, PR China
| | - Baifei Hu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China.
| | - Hongtao Liu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China.
| |
Collapse
|
|
12
|
Klosko RC, Arnold JR, Murphy CV, Brimmer J, Hagy N, Exline MC, McLaughlin E, Elefritz JL. Early onset delirium incidence and risk factors in hematology oncology patients admitted to the intensive care unit: A retrospective cohort study. Int J Crit Illn Inj Sci 2022; 12:190-196. [PMID: 36779215 PMCID: PMC9910111 DOI: 10.4103/ijciis.ijciis_35_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 07/26/2022] [Accepted: 08/02/2022] [Indexed: 12/24/2022] Open
Abstract
Background Delirium occurs frequently in intensive care unit (ICU) patients; however, there are limited data evaluating its impact on critically ill hematology-oncology patients. We aimed to determine the incidence and risk factors for early-onset delirium development in hematology-oncology patients admitted to the ICU. Methods This single-center, retrospective cohort study evaluated the primary outcome of incident delirium within 7 days of ICU admission in adults admitted to the hematology-oncology medical or surgical ICU. Patients with delirium (DEL) were compared to those without (No-DEL) for evaluation of secondary endpoints including hospital mortality, ICU, and hospital length of stay (LOS). Multivariable logistic regression modeling was performed to identify independent risk factors for delirium. Results Delirium occurred in 125 (51.2%) of 244 patients. Inhospital mortality was significantly higher in the DEL vs. No-DEL group (32.8% vs. 15.1%, P = 0.002). Median (1st and 3rd quartiles) ICU and hospital LOS were significantly longer in the delirium group, respectively (6 [4-10] days vs. 3 [2-5] days, P < 0.001, and 21 [14-36] days vs. 12 [8-22] days, P < 0.001). Higher Sequential Organ Failure Assessment score, high-dose corticosteroids, mechanical ventilation (MV), and brain metastases were each independently, associated with an increased delirium risk. Conclusion Hematology-oncology patients admitted to the ICU frequently develop delirium. Consistent with literature in nonhematology-oncology critically ill patients, identified independent risk factors for delirium were MV and organ dysfunction. Risk factors unique to the critically ill hematology-oncology patient population include high-dose corticosteroids and brain metastases. Further research is needed to evaluate strategies to mitigate delirium development in this population based on risk assessment.
Collapse
Affiliation(s)
- Rachel C. Klosko
- Department of Pharmacy Practice, Binghamton University School of Pharmacy and Pharmaceutical Sciences, Johnson City, NY
| | - Joshua R. Arnold
- Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, Ohio, The United States of America
| | - Claire V. Murphy
- Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, Ohio, The United States of America
| | - Jessica Brimmer
- Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, Ohio, The United States of America
| | - Natalie Hagy
- College of Pharmacy, The Ohio State University, Columbus, Ohio, The United States of America
| | - Matthew C. Exline
- Division of Pulmonary Diseases, Critical Care Medicine, and Sleep, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, Ohio, The United States of America
| | - Eric McLaughlin
- Center for Biostatistics, The Ohio State University, Columbus, Ohio, The United States of America
| | - Jessica L. Elefritz
- Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, Ohio, The United States of America
| |
Collapse
|
|
13
|
Bai X, Zhou M. The benefit of bevacizumab therapy in patients with refractory vasogenic edema caused by brain metastasis from lung and colon cancers. Front Oncol 2022; 12:838670. [PMID: 36249059 PMCID: PMC9559828 DOI: 10.3389/fonc.2022.838670] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 09/06/2022] [Indexed: 11/28/2022] Open
Abstract
Objective This retrospective study investigated the efficacy of bevacizumab in refractory brain edema caused by brain metastasis from lung cancer and colon cancer. Methods A total of 72 patients with refractory brain edema were divided into the lung cancer and colon cancer groups according to their primary tumor. All patients received a single bevacizumab treatment for refractory brain edema. MRI was performed 1 week before the treatment and 4 weeks after the treatment. The edema and tumor volumes were calculated using imaging modalities. Results After a single bevacizumab treatment, the refractory brain edema of 61 patients was controlled, and the clinical symptoms of 65 patients were improved. The average edema volume before treatment was 201,708.97 ± 61,426.04 mm3, which has decreased to 116,947.01 ± 43,879.16 mm3 after treatment (P < 0.05). After treatment, the edema index decreased from 25.97 ± 7.15 to 17.32 ± 5.24 (P < 0.05).We found that brain edema was controlled in 40 patients (93.02%) in the lung cancer group and 21 patients (72.41%) in the colon cancer group (P<0.05). In addition, 22 patients (88.00%) in the radiotherapy group achieved edema control, compared to 39 (82.98%) in the non-radiotherapy group (P>0.05). Nine patients experienced hypertension after treatment, two patients exhibited decreased platelet counts, and no hemorrhage cases were observed. Conclusion Bevacizumab can significantly alleviate refractory brain edema, and there is a significant difference in the efficacy of bevacizumab on refractory brain edema caused by brain metastasis from lung and colon cancers.
Collapse
|
|
14
|
Liu C, Wang F, Zhang R. An Acidic Polysaccharide with Anti-Inflammatory Effects from Blackened Jujube: Conformation and Rheological Properties. Foods 2022; 11:foods11162488. [PMID: 36010488 PMCID: PMC9407416 DOI: 10.3390/foods11162488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/13/2022] [Accepted: 08/13/2022] [Indexed: 11/16/2022] Open
Abstract
An acidic polysaccharide fraction (BJP-4) was isolated from blackened jujube, and its advanced structures and anti-inflammatory activity were investigated. X-ray diffraction showed that BJP-4 exhibits both crystalline and amorphous portions. Atomic force microscopy data suggested that it contains a large number of spherical lumps. Circular dichroism and Congo red experiments revealed that it has no triple-helix conformation. In steady shear flow results, the BJP-4 solution was a pseudoplastic non-Newtonian fluid with acid-base stability. BJP-4 (20 mg/mL) showed liquid-like properties (G″ > G′), while it performed weak gel-like behavior at a high concentration (40 mg/mL) (G′ > G″). The anti-inflammatory effects of BJP-4 were further evaluated through in vitro experiments. BJP-4 could down-regulate the over-secretion of inflammatory factors (NO, IL-6, IL-1β, TNF-α, iNOS and COX-2) in RAW264.7 cells due to LPS stimulation. Moreover, it demonstrated that BJP-4 restrained the NF-κB signal pathway by regulating TLR4 expression, reducing IκBα phosphorylation level and NF-κB p65 nuclear translocation. In summary, this present study contributes to the application of blackened jujube polysaccharides in the foods and medicine field.
Collapse
|
|
15
|
Makwana M, Hussain H, Merola JP, Zaben M, Jesurasa AR, Patel C, Leach P. Pre-operative dosing of dexamethasone for the management of children with posterior fossa tumours: are we getting it right? Br J Neurosurg 2022; 36:609-612. [PMID: 35176921 DOI: 10.1080/02688697.2022.2040948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
INTRODUCTION Posterior fossa (PF) tumours are associated with vasogenic oedema causing symptoms of raised intracranial pressure. Preoperatively this is managed with dexamethasone. To minimise steroid related complications, the lowest effective dose should be administered. No neurosurgical guidelines exist for pre-operative dosing of dexamethasone in PF tumours. METHODS A retrospective review was performed of surgically managed cases for patients under 16 years of age between 2013 and 2018 to ascertain the initial dose of dexamethasone with symptomatic PF tumours. RESULTS Thirty-six patients were identified of which 30 notes were available. Sixteen were male. Median age was 6 years (range 10 months - 15 years). Twenty-two (73%) were referrals from DGH and 8 (27%) presented to our neurosurgical centre. All patients presented with symptomatic PF tumours including headache (97%), vomiting (93%), gait disturbance (43%), and nystagmus (17%). Four (13%) had papilloedema. Average initial stat dexamethasone dose was 9.15 mg; 0.31 mg/kg (range 1-16.7 mg; 0.05 - 1.77 mg/kg). Stratified according to weight, average dose (and range) was 8.8 mg; 0.94 mg/kg (1-16.6 mg; 0.13 - 1.77 mg/kg) in those weighing <10 kg; 9.7 mg; 0.66 mg/kg (4-16.7 mg; 0.21 - 1.35 mg/kg) in 10-20 kg; 12.3 mg;0.52 mg/kg (8-16.7 mg; 0.27 - 0.73mg/kg) in 20-30 kg and 7.8 mg; 0.17mg/kg (2-16.7 mg; 0.0 - 0.39 mg/kg) in >30 kg up to a maximum of 16.6 mg in any 24h period. These results suggest that dosage was higher in those children weighing less. PPI was used in 24 (80%) of cases. All doses were reduced after review by the neurosurgical team and a PPI added. CONCLUSION Pre-operative dexamethasone dosing does not always reflect the severity of clinical symptoms for PF tumours. Guidelines are required to correlate clinical symptoms with a suggested suitable dose of dexamethasone to prevent overdose and complications associated with corticosteroid use. We recommend a weight-based regimen as provided by the Food and Drug Administration. The current advice is for 0.02-0.3mg/kg/day in 3-4 divided doses.
Collapse
Affiliation(s)
- Milan Makwana
- Department of Paediatric Neurosurgery, University Hospital of Wales & Noah's Ark Children's Hospital, Cardiff, United Kingdom.,School of Medicine, Neuroscience and Mental Health Research Institute, Institute of Psychological Medicine and Clinical Neurosciences, University Hospital Wales, Cardiff University, Cardiff, United Kingdom
| | - Humaira Hussain
- Department of Paediatric Neurosurgery, University Hospital of Wales & Noah's Ark Children's Hospital, Cardiff, United Kingdom
| | - Joseph P Merola
- Department of Paediatric Neurosurgery, University Hospital of Wales & Noah's Ark Children's Hospital, Cardiff, United Kingdom.,School of Medicine, Neuroscience and Mental Health Research Institute, Institute of Psychological Medicine and Clinical Neurosciences, University Hospital Wales, Cardiff University, Cardiff, United Kingdom
| | - Malik Zaben
- Department of Paediatric Neurosurgery, University Hospital of Wales & Noah's Ark Children's Hospital, Cardiff, United Kingdom.,School of Medicine, Neuroscience and Mental Health Research Institute, Institute of Psychological Medicine and Clinical Neurosciences, University Hospital Wales, Cardiff University, Cardiff, United Kingdom
| | - Anthony R Jesurasa
- Department of Paediatric Neurosurgery, University Hospital of Wales & Noah's Ark Children's Hospital, Cardiff, United Kingdom
| | - Chirag Patel
- Department of Paediatric Neurosurgery, University Hospital of Wales & Noah's Ark Children's Hospital, Cardiff, United Kingdom
| | - Paul Leach
- Department of Paediatric Neurosurgery, University Hospital of Wales & Noah's Ark Children's Hospital, Cardiff, United Kingdom
| |
Collapse
|
|
16
|
M Lewis-Gonzalez J, P Patel M, B Peters K. Multi-joint steroid-induced avascular necrosis in a malignant brain tumor patient. CNS Oncol 2021; 10:CNS78. [PMID: 34636248 PMCID: PMC8610003 DOI: 10.2217/cns-2021-0006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Avascular necrosis (AVN) is a rare but serious adverse event associated with the use of corticosteroids for long durations or at high doses. This case report describes a 47-year-old female patient with low-grade astrocytoma who was initiated on low-dose dexamethasone for symptom management. The patient developed joint pain 1 year after steroid exposure, then was found to have AVN of the hip followed by multiple other joints. This case report highlights the extent to which AVN can occur in patients with brain tumors following a short course of low-dose corticosteroids. Careful evaluation of and monitoring for the development of AVN should occur frequently in patients with brain tumors given the frequent use of corticosteroids for symptom management in this population.
Collapse
Affiliation(s)
- Jessica M Lewis-Gonzalez
- Department of Pharmacy, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87106, USA
| | - Mallika P Patel
- Department of Pharmacy, Duke University Medical Center, Durham, NC 27710, USA
| | - Katherine B Peters
- Department of Neurosurgery & Neurology, Duke University Medical Center, Durham, NC 27710, USA
| |
Collapse
|
|
17
|
Primary Central Nervous System Lymphoma in Elderly Patients: Management and Perspectives. Cancers (Basel) 2021; 13:cancers13143479. [PMID: 34298693 PMCID: PMC8303711 DOI: 10.3390/cancers13143479] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 07/05/2021] [Accepted: 07/08/2021] [Indexed: 12/29/2022] Open
Abstract
The management of elderly patients suffering from primary central nervous system (CNS) lymphoma, who represent a rapidly growing population, is challenging. Despite the advances made in PCNSL treatment, the prognosis in older patients remains unsatisfactory. The high risk of systemic and CNS toxicity induced by a high-dose chemotherapy regimen and radiation therapy, respectively, limits the use of consolidation phase treatments in elderly patients and contributes to the poor outcome of these patients. Here, we review the current treatment strategies and ongoing trials proposed for elderly PCNSL patients.
Collapse
|
|
18
|
Scheichel F, Marhold F, Pinggera D, Kiesel B, Rossmann T, Popadic B, Woehrer A, Weber M, Kitzwoegerer M, Geissler K, Dopita A, Oberndorfer S, Pfisterer W, Freyschlag CF, Widhalm G, Ungersboeck K, Roessler K. Influence of preoperative corticosteroid treatment on rate of diagnostic surgeries in primary central nervous system lymphoma: a multicenter retrospective study. BMC Cancer 2021; 21:754. [PMID: 34187419 PMCID: PMC8243818 DOI: 10.1186/s12885-021-08515-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 06/15/2021] [Indexed: 12/02/2022] Open
Abstract
Background Corticosteroid therapy (CST) prior to biopsy may hinder histopathological diagnosis in primary central nervous system lymphoma (PCNSL). Therefore, preoperative CST in patients with suspected PCNSL should be avoided if clinically possible. The aim of this study was thus to analyze the difference in the rate of diagnostic surgeries in PCNSL patients with and without preoperative CST. Methods A multicenter retrospective study including all immunocompetent patients diagnosed with PCNSL between 1/2004 and 9/2018 at four neurosurgical centers in Austria was conducted and the results were compared to literature. Results A total of 143 patients were included in this study. All patients showed visible contrast enhancement on preoperative MRI. There was no statistically significant difference in the rate of diagnostic surgeries with and without preoperative CST with 97.1% (68/70) and 97.3% (71/73), respectively (p = 1.0). Tapering and pause of CST did not influence the diagnostic rate. Including our study, there are 788 PCNSL patients described in literature with an odds ratio for inconclusive surgeries after CST of 3.3 (CI 1.7–6.4). Conclusions Preoperative CST should be avoided as it seems to diminish the diagnostic rate of biopsy in PCNSL patients. Yet, if CST has been administered preoperatively and there is still a contrast enhancing lesion to target for biopsy, surgeons should try to keep the diagnostic delay to a minimum as the likelihood for acquiring diagnostic tissue seems sufficiently high.
Collapse
Affiliation(s)
- Florian Scheichel
- Karl Landsteiner University of Health Sciences, Krems, Austria.,Department of Neurosurgery, University Hospital St. Poelten, Dunant-Platz 1, 3100, St. Poelten, Austria
| | - Franz Marhold
- Karl Landsteiner University of Health Sciences, Krems, Austria. .,Department of Neurosurgery, University Hospital St. Poelten, Dunant-Platz 1, 3100, St. Poelten, Austria.
| | - Daniel Pinggera
- Department of Neurosurgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Barbara Kiesel
- Department of Neurosurgery, Medical University Vienna, Vienna, Austria
| | - Tobias Rossmann
- Department of Neurosurgery, Donauspital SMZ-Ost, Vienna, Austria.,Department of Neurosurgery, Neuromed Campus, Kepler University Hospital, Johannes Kepler University, Linz, Austria
| | - Branko Popadic
- Karl Landsteiner University of Health Sciences, Krems, Austria.,Department of Neurosurgery, University Hospital St. Poelten, Dunant-Platz 1, 3100, St. Poelten, Austria
| | - Adelheid Woehrer
- Institute of Neurology, Medical University Vienna, Vienna, Austria
| | - Michael Weber
- Department of Research Management, Karl Landsteiner University of Health Sciences, Krems, Austria
| | - Melitta Kitzwoegerer
- Karl Landsteiner University of Health Sciences, Krems, Austria.,Department of Pathology, University Hospital St. Poelten, St.Poelten, Austria
| | | | - Astrid Dopita
- Institute for Pathology and Microbiology, Donauspital SMZ-Ost, Vienna, Austria
| | - Stefan Oberndorfer
- Karl Landsteiner University of Health Sciences, Krems, Austria.,Department of Neurology, University Hospital St. Poelten, St.Poelten, Austria
| | | | | | - Georg Widhalm
- Department of Neurosurgery, Medical University Vienna, Vienna, Austria
| | - Karl Ungersboeck
- Karl Landsteiner University of Health Sciences, Krems, Austria.,Department of Neurosurgery, University Hospital St. Poelten, Dunant-Platz 1, 3100, St. Poelten, Austria
| | - Karl Roessler
- Department of Neurosurgery, Medical University Vienna, Vienna, Austria
| |
Collapse
|
|
19
|
Liquid Biopsy and Other Non-Invasive Diagnostic Measures in PCNSL. Cancers (Basel) 2021; 13:cancers13112665. [PMID: 34071407 PMCID: PMC8198992 DOI: 10.3390/cancers13112665] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 05/21/2021] [Accepted: 05/25/2021] [Indexed: 12/11/2022] Open
Abstract
Simple Summary Primary central nervous system lymphoma (PCNSL) is an uncommon disease accounting for around 3% of primary CNS tumors. PCNSL exhibits aggressive clinical behavior and has an overall poor prognosis. The clinical presentation is variable, and there are no specific symptoms. Despite progress in radiographic neuroimaging, stereotactic brain biopsy remains obligatory for definitive diagnosis. Advanced standard diagnostics, including CSF cytology and flow cytometry, have limited sensitivity. Accordingly, there is an urgent need to improve the diagnostic tools for PCNSL, including novel non-invasive procedures. The aim of this review is to present and discuss modern methods that have the potential to contribute standard clinical diagnostics within the next few years. Abstract Primary central nervous system lymphoma is a rare but highly aggressive form of non-Hodgkin lymphoma that remains confined to the CNS neuroaxis. The diagnosis of PCNSL requires a high level of suspicion as clinical presentation varies depending on the involved CNS areas. Neurological symptoms and MRI findings may mimic gliomas, demyelinating lesions, or infectious and granulomatous diseases. Almost all PCNSL patients undergo invasive surgical procedures for definite diagnosis. Stereotactic biopsy is still the gold standard in achieving a diagnostic accuracy of 73–97%. Both the potential procedural morbidity and mortality, as well as the time to definite histopathologic diagnosis resulting in delays of treatment initiation, have to be considered. On the contrary, minimally invasive procedures, such as MRI, CSF cytology, and flow cytometry, still have limited value due to inferior specificity and sensitivity. Hence, novel diagnostic approaches, including mutation analyses (MYD88) in circulating tumor DNA (ctDNA) and the determination of microRNAs (miR-21, miR-19b, and miR-92) as well as cytokine levels (IL10 and IL6) in blood, cerebrospinal fluid (CSF), and vitreous fluid (VRF), move into the focus of investigation to facilitate the diagnosis of PCNSL. In this review, we outline the most promising approaches that are currently under clinical consideration.
Collapse
|
|
20
|
Wielgat P, Wawrusiewicz-Kurylonek N, Czarnomysy R, Rogowski K, Bielawski K, Car H. The Paired Siglecs in Brain Tumours Therapy: The Immunomodulatory Effect of Dexamethasone and Temozolomide in Human Glioma In Vitro Model. Int J Mol Sci 2021; 22:ijms22041791. [PMID: 33670244 PMCID: PMC7916943 DOI: 10.3390/ijms22041791] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 02/04/2021] [Accepted: 02/09/2021] [Indexed: 12/14/2022] Open
Abstract
The paired sialic acid-binding immunoglobulin like lectins (Siglecs) are characterized by similar cellular distribution and ligand recognition but opposing signalling functions attributed to different intracellular sequences. Since sialic acid—Siglec axis are known to control immune homeostasis, the imbalance between activatory and inhibitory mechanisms of glycan-dependent immune control is considered to promote pathology. The role of sialylation in cancer is described, however, its importance in immune regulation in gliomas is not fully understood. The experimental and clinical observation suggest that dexamethasone (Dex) and temozolomide (TMZ), used in the glioma management, alter the immunity within the tumour microenvironment. Using glioma-microglia/monocytes transwell co-cultures, we investigated modulatory action of Dex/TMZ on paired Siglecs. Based on real-time PCR and flow cytometry, we found changes in SIGLEC genes and their products. These effects were accompanied by altered cytokine profile and immune cells phenotype switching measured by arginases expression. Additionally, the exposure to Dex or TMZ increased the binding of inhibitory Siglec-5 and Siglec-11 fusion proteins to glioma cells. Our study suggests that the therapy-induced modulation of the interplay between sialoglycans and paired Siglecs, dependently on patient’s phenotype, is of particular signification in the immune surveillance in the glioma management and may be useful in glioma patient’s therapy plan verification.
Collapse
Affiliation(s)
- Przemyslaw Wielgat
- Department of Clinical Pharmacology, Medical University of Bialystok, Waszyngtona 15A, 15-274 Bialystok, Poland;
- Correspondence: ; Tel.: +48-85-7450-647
| | | | - Robert Czarnomysy
- Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilińskiego 1, 15-089 Bialystok, Poland; (R.C.); (K.B.)
| | - Karol Rogowski
- Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna 37, 15-295 Bialystok, Poland;
| | - Krzysztof Bielawski
- Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilińskiego 1, 15-089 Bialystok, Poland; (R.C.); (K.B.)
| | - Halina Car
- Department of Clinical Pharmacology, Medical University of Bialystok, Waszyngtona 15A, 15-274 Bialystok, Poland;
- Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna 37, 15-295 Bialystok, Poland;
| |
Collapse
|
|
21
|
Roth P, Pace A, Le Rhun E, Weller M, Ay C, Cohen-Jonathan Moyal E, Coomans M, Giusti R, Jordan K, Nishikawa R, Winkler F, Hong JT, Ruda R, Villà S, Taphoorn MJB, Wick W, Preusser M. Neurological and vascular complications of primary and secondary brain tumours: EANO-ESMO Clinical Practice Guidelines for prophylaxis, diagnosis, treatment and follow-up. Ann Oncol 2021; 32:171-182. [PMID: 33246022 DOI: 10.1016/j.annonc.2020.11.003] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 11/03/2020] [Accepted: 11/06/2020] [Indexed: 02/08/2023] Open
Affiliation(s)
- P Roth
- Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Zurich, Switzerland
| | - A Pace
- Neuroncology Unit, IRCCS Regina Elena Cancer Institute, Rome, Italy
| | - E Le Rhun
- Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Zurich, Switzerland; Université Lille, U-1192, Lille, France; Inserm, U-1192, Lille, France; Centre Hospitalier Universitaire CHU, Lille, General and Stereotaxic Neurosurgery Service, Lille, France; Oscar Lambret Center, Breast Cancer Department, Lille, France
| | - M Weller
- Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Zurich, Switzerland
| | - C Ay
- Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Vienna, Austria
| | - E Cohen-Jonathan Moyal
- Radiation Oncology Department, Institut Claudius Regaud, Université Paul Sabatier, Toulouse, France; Institut Universitaire du Cancer de Toulouse IUCT Oncopole, Toulouse, France
| | - M Coomans
- Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
| | - R Giusti
- Medical Oncology Unit, Azienda Ospedaliero Universitaria Sant'Andrea, Rome, Italy
| | - K Jordan
- Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany
| | - R Nishikawa
- Department of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan
| | - F Winkler
- Department of Neurology and Neurooncology Program, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany
| | - J T Hong
- Department of Neurosurgery, Eunpyeong St. Mary's Hospital, Seoul, The Catholic University of Korea, Republic of Korea
| | - R Ruda
- Department of Neuro-Oncology, City of Health and Science and University of Turin, Turin, Italy
| | - S Villà
- Catalan Institute of Oncology, HU Germans Trias, Badalona, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - M J B Taphoorn
- Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands; Department of Neurology, Haaglanden Medical Center, The Hague, The Netherlands
| | - W Wick
- Department of Neurology and Neurooncology Program, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany
| | - M Preusser
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
|
22
|
Grabowski MM, Sankey EW, Ryan KJ, Chongsathidkiet P, Lorrey SJ, Wilkinson DS, Fecci PE. Immune suppression in gliomas. J Neurooncol 2021; 151:3-12. [PMID: 32542437 PMCID: PMC7843555 DOI: 10.1007/s11060-020-03483-y] [Citation(s) in RCA: 189] [Impact Index Per Article: 47.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 04/03/2020] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The overall survival in patients with gliomas has not significantly increased in the modern era, despite advances such as immunotherapy. This is in part due to their notorious ability to suppress local and systemic immune responses, severely restricting treatment efficacy. METHODS We have reviewed the preclinical and clinical evidence for immunosuppression seen throughout the disease process in gliomas. This review aims to discuss the various ways that brain tumors, and gliomas in particular, co-opt the body's immune system to evade detection and ensure tumor survival and proliferation. RESULTS A multitude of mechanisms are discussed by which neoplastic cells evade detection and destruction by the immune system. These include tumor-induced T-cell and NK cell dysfunction, regulatory T-cell and myeloid-derived suppressor cell expansion, M2 phenotypic transformation in glioma-associated macrophages/microglia, upregulation of immunosuppressive glioma cell surface factors and cytokines, tumor microenvironment hypoxia, and iatrogenic sequelae of immunosuppressive treatments. CONCLUSIONS Gliomas create a profoundly immunosuppressive environment, both locally within the tumor and systemically. Future research should aim to address these immunosuppressive mechanisms in the effort to generate treatment options with meaningful survival benefits for this patient population.
Collapse
Affiliation(s)
- Matthew M Grabowski
- Duke Brain Tumor Immunotherapy Program, Duke University Medical Center, 303 Research Drive, 220 Sands Bldg, Durham, NC, 27710, USA
| | - Eric W Sankey
- Duke Brain Tumor Immunotherapy Program, Duke University Medical Center, 303 Research Drive, 220 Sands Bldg, Durham, NC, 27710, USA
| | - Katherine J Ryan
- Duke Brain Tumor Immunotherapy Program, Duke University Medical Center, 303 Research Drive, 220 Sands Bldg, Durham, NC, 27710, USA
| | - Pakawat Chongsathidkiet
- Duke Brain Tumor Immunotherapy Program, Duke University Medical Center, 303 Research Drive, 220 Sands Bldg, Durham, NC, 27710, USA
| | - Selena J Lorrey
- Duke Brain Tumor Immunotherapy Program, Duke University Medical Center, 303 Research Drive, 220 Sands Bldg, Durham, NC, 27710, USA
| | - Daniel S Wilkinson
- Duke Brain Tumor Immunotherapy Program, Duke University Medical Center, 303 Research Drive, 220 Sands Bldg, Durham, NC, 27710, USA
| | - Peter E Fecci
- Duke Brain Tumor Immunotherapy Program, Duke University Medical Center, 303 Research Drive, 220 Sands Bldg, Durham, NC, 27710, USA.
| |
Collapse
|
|
23
|
Rauschenbach L, Kebir S, Radbruch A, Darkwah Oppong M, Gembruch O, Teuber-Hanselmann S, Gielen GH, Scheffler B, Glas M, Sure U, Lemonas E. Challenging Implications of Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids Syndrome with an Atypical Presentation: Report of Two Cases. World Neurosurg 2020; 143:507-512.e1. [PMID: 32711135 DOI: 10.1016/j.wneu.2020.07.123] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 07/14/2020] [Accepted: 07/16/2020] [Indexed: 11/18/2022]
Abstract
BACKGROUND Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an increasingly recognized neuroinflammatory syndrome that predominantly affects the pontine and cerebellar brain structures. Characteristically, patients will develop glucocorticoid-responsive brainstem disorders, demonstrate pontocerebellar contrast enhancement on magnetic resonance imaging (MRI), and exhibit an angiocentric, lymphocytic infiltrate in brain biopsies. We have presented and discussed 2 novel and challenging cases of CLIPPERS syndrome to highlight the clinical and radiological diversity of the syndrome. CASE DESCRIPTION The first case was of a 66-year-old male patient who had presented with dizziness, headaches, gait disturbances, mild cognitive impairment, and visual field loss to the left side. MRI revealed 1 cerebellar and 2 occipital contrast-enhancing lesions that were suspicious for intracerebral metastases. The second case was of a 53-year-old male patient who had presented with temporal lobe epilepsy, anomic aphasia, and mild cognitive impairment. MRI demonstrated 4 contrast-enhancing lesions in the pons, temporal lobe, and thalamus that were suspicious for intracerebral lymphoma. Because of the radiological presentation, neoplastic disease was the most plausible diagnosis for both patients. However, repeated biopsies ruled out tumor manifestation, and the findings were finally consistent with CLIPPERS syndrome. The significant and long-lasting response to immunosuppressive treatment confirmed the diagnosis. CONCLUSIONS In both cases, the characteristics of CLIPPERS syndrome imitated malignant tumor growth. This scenario can be challenging to clinicians and necessitates inclusion of this neuroinflammatory syndrome in the differential diagnosis of neuro-oncological disease.
Collapse
Affiliation(s)
- Laurèl Rauschenbach
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Essen, Germany; Division of Translational Neurooncology, West German Cancer Center, German Cancer Consortium Partner Site, University Hospital Essen, Essen, Germany.
| | - Sied Kebir
- Division of Translational Neurooncology, West German Cancer Center, German Cancer Consortium Partner Site, University Hospital Essen, Essen, Germany; Division of Clinical Neurooncology, Department of Neurology, University Hospital Essen, Essen, Germany
| | - Alexander Radbruch
- Division of Neuroradiology, Institute for Diagnostic and Interventional Radiology, University Hospital Essen, Essen, Germany
| | - Marvin Darkwah Oppong
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Essen, Germany
| | - Oliver Gembruch
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Essen, Germany
| | | | - Gerrit H Gielen
- Institute of Neuropathology, University Hospital Bonn, Bonn, Germany
| | - Björn Scheffler
- Division of Translational Neurooncology, West German Cancer Center, German Cancer Consortium Partner Site, University Hospital Essen, Essen, Germany
| | - Martin Glas
- Division of Translational Neurooncology, West German Cancer Center, German Cancer Consortium Partner Site, University Hospital Essen, Essen, Germany; Division of Clinical Neurooncology, Department of Neurology, University Hospital Essen, Essen, Germany
| | - Ulrich Sure
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Essen, Germany
| | - Elias Lemonas
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Essen, Germany
| |
Collapse
|
|
24
|
Carminucci A, Tejero R, Huang Y, Danish S, Friedel RH, Foty R. Teaching an Old Drug New Tricks: Dexamethasone as an In Vivo Inhibitor of Glioblastoma Dispersal. Cureus 2020; 12:e7749. [PMID: 32455066 PMCID: PMC7243068 DOI: 10.7759/cureus.7749] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Identifying drugs that can mitigate dispersal of glioblastoma cells, particularly after patients undergo radiotherapy and concomitant chemotherapy, may increase the length of time to recurrence and improve overall survival. Previous studies have shown that dexamethasone (Dex), a drug currently used to treat brain tumor-related edema, which is tapered immediately after the edema has resolved, induces fibronectin matrix assembly (FNMA) and reduces dispersal of primary human glioblastoma multiforme (GBM) cells in vitro and ex vivo. Here, we utilized an in vivo mouse retina dispersal assay to demonstrate that Dex also inhibits dispersal in vivo. We show that 1) Dex significantly reduces z-axis penetration of glioblastoma cells into mouse retina; 2) treatment alters the morphology of dispersal; 3) without Dex, the presence of fibronectin increases dispersal; 4) treatment activates in vivo FNMA by glioblastoma cells, leading to the containment of the tumor mass; and 5) Dex-mediated activation of FNMA is fibronectin dose-dependent. Dispersal inhibition could be achieved at human equivalent doses as low as 1 mg/day, a dose significantly lower than currently used to reduce edema. This is the first step towards future studies in which patients can be potentially maintained on low-dose dexamethasone therapy with the aim of increasing the time between initial resection and recurrence.
Collapse
Affiliation(s)
- Arthur Carminucci
- Neurosurgery, Rutgers Robert Wood Johnson Medical School, Piscataway, USA
| | - Rut Tejero
- Neuroscience, Mount Sinai School of Medicine, New York, USA
| | - Yong Huang
- Neuroscience, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Shabbar Danish
- Neurosurgery, Rutgers Robert Wood Johnson Medical School, Piscataway, USA
| | | | - Ramsey Foty
- General Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, USA
| |
Collapse
|
|
25
|
Gessler F, Bernstock JD, Behmanesh B, Brunnberg U, Harter P, Ye D, Friedman GK, Hansmann ML, Wagner M, Seifert V, Weise L, Marquardt G. The Impact of Early Corticosteroid Pretreatment Before Initiation of Chemotherapy in Patients With Primary Central Nervous System Lymphoma. Neurosurgery 2020; 85:264-272. [PMID: 30016483 DOI: 10.1093/neuros/nyy272] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Accepted: 05/27/2018] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND The optimal timing of corticosteroid (CS) treatment in patients with primary central nervous system (CNS) lymphoma (PCNSL) remains controversial. While poor clinical presentation may justify early treatment with CS, this may ultimately result in reduced concentrations of chemotherapeutic agents via perturbations in the permeability of the blood-brain barrier. OBJECTIVE To investigate whether early CS exposure is associated with beneficial outcomes and/or reduced occurrence of adverse events as opposed to delayed/concomitant administration. METHODS Herein we performed a retrospective observational analysis using patients that were prospectively entered into a database. All patients whom were admitted to the University Hospital between 2009 and 2015 with newly diagnosed PCNSL were included within our study. RESULTS Our cohort included 50 consecutive patients diagnosed with PCNSL; of these, in 30 patients CS administration was initiated prior to chemotherapy (early), whilst in the remaining 20 patients CS administration was initiated concomitantly with their chemotherapeutic regimen (concomitant). Within the early vs concomitant CS administration groups, no significant differences were observed with regard to progression-free survival (PFS) (P = .81), overall survival (OS) (P = .75), or remission (P = .68; odds ratio 0.76 and confidence interval [95%] 0.22-2.71). Critically, the timing of CS initiation was not associated with either PFS (P = .81) or PFS (P = .75). CONCLUSION Early CS administration was not associated with a deterioration in response to chemotherapy, PFS, or OS. As such, administration of CS prior to initiation of chemotherapy is both reasonable and safe for patients with newly diagnosed PCNSL.
Collapse
Affiliation(s)
- Florian Gessler
- Department of Neurosurgery, University Hospital Frankfurt, Goethe-University Frankfurt, Schleusenweg, Frankfurt, Germany
| | - Joshua D Bernstock
- Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS/NIH), Bethesda, Maryland
| | - Bedjan Behmanesh
- Department of Neurosurgery, University Hospital Frankfurt, Goethe-University Frankfurt, Schleusenweg, Frankfurt, Germany
| | - Uta Brunnberg
- Department of Internal Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt, Germany
| | - Patrick Harter
- Institute of Neurology (Edinger-Institute), Goethe-University Frankfurt, Frankfurt, Germany
| | - Daniel Ye
- Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS/NIH), Bethesda, Maryland
| | - Gregory K Friedman
- Neuro-Oncology Program, Department of Pediatrics, University of Alabama, Birmingham, Alabama
| | - Martin-Leo Hansmann
- Dr Senckenberg Institute of Pathology, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt, Germany
| | - Marlies Wagner
- Institute of Neuroradiology, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt, Germany
| | - Volker Seifert
- Department of Neurosurgery, University Hospital Frankfurt, Goethe-University Frankfurt, Schleusenweg, Frankfurt, Germany
| | - Lutz Weise
- Department of Neurosurgery, University Hospital Frankfurt, Goethe-University Frankfurt, Schleusenweg, Frankfurt, Germany
| | - Gerhard Marquardt
- Department of Neurosurgery, University Hospital Frankfurt, Goethe-University Frankfurt, Schleusenweg, Frankfurt, Germany
| |
Collapse
|
|
26
|
Berghoff AS, Breckwoldt MO, Riedemann L, Karimian-Jazi K, Loew S, Schlieter F, Furtner J, Cinci M, Thomas M, Strowitzki MJ, Marmé F, Michel LL, Schmidt T, Jäger D, Bendszus M, Preusser M, Wick W, Winkler F. Bevacizumab-based treatment as salvage therapy in patients with recurrent symptomatic brain metastases. Neurooncol Adv 2020; 2:vdaa038. [PMID: 32642693 PMCID: PMC7212911 DOI: 10.1093/noajnl/vdaa038] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Background Salvage treatment for recurrent brain metastases (BM) of solid cancers is challenging due to the high symptomatic burden and the limited local treatment options. Methods Patients with recurrent BM with no option for further local therapies were retrospectively identified from BM databases. Bevacizumab-based treatment was initiated as a salvage treatment. Radiological imaging before and after bevacizumab-based treatment was reevaluated for treatment response using the Response Assessment in Neuro-Oncology (RANO) BM criteria. Results Twenty-two patients (36.4% male) with recurrent BM from breast cancer (40.9%), colorectal cancer (31.8%), or lung cancer (27.3%) were identified. Previous BM-directed therapies were radiosurgery in 16/22 (72.7%) patients, whole-brain radiotherapy in 8/22 (36.4%), and neurosurgical resection in 11/22 (50.0%). Time since BM diagnosis to initiation of bevacizumab treatment was 16.5 months. Of 22 patients 14 (63.6%) received concurrent systemic therapies. Neurological symptom improvement could be achieved in 14/22 (63.6%) and stabilization in 6/22 (27.3%) patients, resulting in a clinical benefit in 20/22 (90.9%) patients. Steroids could be reduced or stopped in 15/22 (68.2%) patients. Rate of improvement on T1-weighted imaging was 15/19 (78.9%; median reduction: -26.0% ± 32.9) and 19/20 (95%; median reduction: -36.2% ± 22.2) on T2-weighted FLAIR imaging. According to RANO-BM best response was partial response in 7/19 (36.8%), stable disease in 9/19 (47.3%), and progressive disease in 3/19 (15.7%) patients. Median CNS-specific progression-free survival was 8 months and median overall survival after initiation of bevacizumab treatment was 17 months. Conclusions Bevacizumab-based treatment had clinically relevant intracranial activity in the vast majority of patients suffering from recurrent, symptomatic BM. The data supports a prospective clinical trial of bevacizumab as a salvage treatment in BM.
Collapse
Affiliation(s)
- Anna Sophie Berghoff
- Department of Medicine I, Medical University of Vienna, Vienna, Austria.,Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Clinical Cooperation Unit Neuro-Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | | | - Lars Riedemann
- Clinical Cooperation Unit Neuro-Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.,Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany
| | | | - Sarah Loew
- Clinical Cooperation Unit Neuro-Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.,Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany
| | - Franziska Schlieter
- Department of Medicine I, Medical University of Vienna, Vienna, Austria.,Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Julia Furtner
- Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Marc Cinci
- Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany
| | - Michael Thomas
- Department of Thoracic Oncology, University Hospital Heidelberg and Translational Lung Research Center Heidelberg, Heidelberg, Germany
| | - Moritz J Strowitzki
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Frederik Marmé
- National Center for Tumor Disease, Gynecologic Oncology, University Hospital Heidelberg, Heidelberg, Germany
| | - Laura L Michel
- National Center for Tumor Disease, Gynecologic Oncology, University Hospital Heidelberg, Heidelberg, Germany
| | - Thomas Schmidt
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Dirk Jäger
- Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany
| | - Martin Bendszus
- Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Matthias Preusser
- Department of Medicine I, Medical University of Vienna, Vienna, Austria.,Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Wick
- Clinical Cooperation Unit Neuro-Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.,Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany
| | - Frank Winkler
- Clinical Cooperation Unit Neuro-Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.,Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany
| |
Collapse
|
|
27
|
Provider views on perioperative steroid use for patients with newly diagnosed pediatric brain tumors. J Neurooncol 2020; 147:205-212. [PMID: 32026434 DOI: 10.1007/s11060-020-03416-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 01/29/2020] [Indexed: 10/25/2022]
Abstract
PURPOSE Cerebral edema from brain tumors can cause neurological impairment. Steroids treat edema but with possible adverse effects. We surveyed providers regarding steroid use in newly diagnosed patients with brain tumors to determine if practices are standard or markedly variable. METHODS An anonymous voluntary online survey was sent to members of neuro-oncology consortiums. Four clinical scenarios were provided and questions regarding initiation of steroids, type, dose, formulation, and duration were asked. Demographic information was collected. RESULTS 369 providers received the survey, 76 responded (20.6% response rate). The proportion of providers who would start steroids significantly differed among scenarios (scenario 1 vs 2, p < 0.001; 2 vs 3, p < 0.001; 1 vs 3, p < 0.001). 75 (98.7%) providers would start steroids for vasogenic edema (scenario 1) and 55 (72.4%) for obstructive hydrocephalus (scenario 2). 16 (21.1%) would start steroids for vasogenic edema but not obstructive hydrocephalus. The odds of choosing to start steroids in patients with obstructive hydrocephalus were 7.59 times more (95% CI: 2.29, 25.13) if providers felt symptoms would improve within 24 h. All would use dexamethasone. A significant difference was seen between the proportion of providers who would give a loading dose if vasogenic edema with neurological deficits were noted versus vasogenic edema alone (57.9% vs 43.4%; p = 0.002). CONCLUSIONS These results suggest that providers recommend dexamethasone for patients with vasogenic edema and obstructive hydrocephalus. Variability remains with dosing schedule. Further studies are needed to identify the most appropriate use of steroids for newly diagnosed CNS tumor patients with the goal to create steroid management guidelines.
Collapse
|
|
28
|
Pergakis M, Badjatia N, Chaturvedi S, Cronin CA, Kimberly WT, Sheth KN, Simard JM. BIIB093 (IV glibenclamide): an investigational compound for the prevention and treatment of severe cerebral edema. Expert Opin Investig Drugs 2019; 28:1031-1040. [PMID: 31623469 DOI: 10.1080/13543784.2019.1681967] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Introduction: Brain swelling due to edema formation is a major cause of neurological deterioration and death in patients with large hemispheric infarction (LHI) and severe traumatic brain injury (TBI), especially contusion-TBI. Preclinical studies have shown that SUR1-TRPM4 channels play a critical role in edema formation and brain swelling in LHI and TBI. Glibenclamide, a sulfonylurea drug and potent inhibitor of SUR1-TRPM4, was reformulated for intravenous injection, known as BIIB093.Areas covered: We discuss the findings from Phase 2 clinical trials of BIIB093 in patients with LHI (GAMES-Pilot and GAMES-RP) and from a small Phase 2 clinical trial in patients with TBI. For the GAMES trials, we review data on objective biological variables, adjudicated edema-related endpoints, functional outcomes, and mortality which, despite missing the primary endpoint, supported the initiation of a Phase 3 trial in LHI (CHARM). For the TBI trial, we review data on MRI measures of edema and the initiation of a Phase 2 trial in contusion-TBI (ASTRAL).Expert opinion: Emerging clinical data show that BIIB093 has the potential to transform our management of patients with LHI, contusion-TBI and other conditions in which swelling leads to neurological deterioration and death.
Collapse
Affiliation(s)
- Melissa Pergakis
- Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Neeraj Badjatia
- Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Seemant Chaturvedi
- Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Carolyn A Cronin
- Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - W Taylor Kimberly
- Division of Neurocritical Care and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Kevin N Sheth
- Division of Neurocritical Care, Department of Neurology, Yale University School of Medicine, New Haven, CT, USA
| | - J Marc Simard
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA
| |
Collapse
|
|
29
|
Pantelidis P, Tsitsopoulos PP, Pappa E, Theologou E, Karanikolas N, Drosos C, Tsonidis C. The effect of diabetes mellitus on in-hospital hyperglycemia, length of stay and survival in patients with brain tumor receiving dexamethasone: A descriptive and comparative analysis. Clin Neurol Neurosurg 2019; 184:105450. [PMID: 31376773 DOI: 10.1016/j.clineuro.2019.105450] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 07/15/2019] [Accepted: 07/17/2019] [Indexed: 12/16/2022]
Abstract
OBJECTIVES To perform a comparative analysis on the impact of Type 2 Diabetes Mellitus (DM) on in-hospital hyperglycemia, length of stay (LOS) and survival of patients suffering from brain tumor who receive dexamethasone. PATIENTS AND METHODS Patients with brain tumor hospitalized in a Neurosurgery department between 2011 and 2018, were studied. Data referring to medical history, clinical characteristics and in-hospital survival was collected and analyzed. Morning plasma glucose levels (PGL) were obtained for seven consecutive days after the start of dexamethasone. RESULTS Fifty-six patients were identified. Of them, 21 (37.5%) were diabetic. During dexamethasone administration, a difference in morning PGL values during different days was noted (p = 0.003). No difference in glucose levels among different glucocorticoid doses was seen. DM was associated with higher average PGL (aMPGL), calculated as the mean of morning PGL values for the last six days (p = 0.001) and with higher rates of persistent hyperglycemia (p = 0.002). The change of aMPGL from the morning PGL value of day one did not differ between the two cohorts (p = 0.729). DM neither affected LOS nor in-hospital survival (p = 0.745 & p = 0.438, respectively). CONCLUSION Although morning glucose values were higher in diabetic, compared to non-diabetic patients, their change from day one was similar between the two cohorts. LOS and in-hospital survival were not affected by DM.
Collapse
Affiliation(s)
- Panteleimon Pantelidis
- Department of Neurosurgery, Hippokration General Hospital, Aristotle University School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece.
| | - Parmenion P Tsitsopoulos
- Department of Neurosurgery, Hippokration General Hospital, Aristotle University School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece
| | - Eleni Pappa
- Department of Neurosurgery, Hippokration General Hospital, Aristotle University School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece
| | - Elpida Theologou
- Department of Neurosurgery, Hippokration General Hospital, Aristotle University School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece
| | - Nikolaos Karanikolas
- Department of Neurosurgery, Hippokration General Hospital, Aristotle University School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece
| | - Christos Drosos
- Department of Neurosurgery, Hippokration General Hospital, Aristotle University School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece
| | - Christos Tsonidis
- Department of Neurosurgery, Hippokration General Hospital, Aristotle University School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece
| |
Collapse
|
|
30
|
Altinoz MA, Nalbantoglu J, Ozpinar A, Emin Ozcan M, Del Maestro RF, Elmaci I. From epidemiology and neurodevelopment to antineoplasticity. Medroxyprogesterone reduces human glial tumor growth in vitro and C6 glioma in rat brain in vivo. Clin Neurol Neurosurg 2018; 173:20-30. [PMID: 30055402 DOI: 10.1016/j.clineuro.2018.07.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Revised: 07/03/2018] [Accepted: 07/13/2018] [Indexed: 11/17/2022]
Abstract
OBJECTIVE Glial tumor growth may accelerate during gestation, but epidemiological studies consistently demonstrated that parousity reduces life long risk of glial tumors. Pregnancy may also accelerate growth of medulloblastoma and meningioma, but parousity does not confer protection against these tumors. We were the first to show that medroxyprogesterone acetate (MPA) reduces rat C6 glioma growth in vitro. Now we aimed to determine the effects of MPA on human brain cancers (particularly glioblastoma) in vitro and C6 glioma in vivo. PATIENTS AND METHODS We evaluated the effects of MPA on: i) monolayer growth of human U87 and U251 glioblastoma, ii) 3D-spheroid growth and invasion of C6 rat glioma and human U251 glioma, iii) interactions with PI3-Kinase inhibitors and coxsackie-adenovirus receptor (CAR) in modifying 3D-spheroid invasion of glioma. RESULTS MPA at low doses (3.25-13 μM) insignificantly stimulated and at high doses (above 52 μM) strongly suppressed the growth of human U87 and U251 cells in vitro. MPA also binds to glucocorticoid receptors similar to dexamethasone (Dex) and unexpectedly, PI3-Kinase inhibitors at low doses suppressed anti-invasive efficacies of MPA and Dex. MPA exerted higher invasion-inhibitory effects on CAR-expressing human glioma cells. Lastly, MPA suppressed growth of C6 glioma implanted into rat brain. CONCLUSION Progesterone analogues deserve to be studied in future experimental models of high grade glial brain tumors.
Collapse
Affiliation(s)
- Meric A Altinoz
- Neuroacademy Research Group, Istanbul, Turkey; Department of Psychiatry, Maastricht University, Holland, Netherlands.
| | - Josephine Nalbantoglu
- Department of Neuroimmunology, Montreal Neurological Institute, McGill University, Montreal, Canada
| | - Aysel Ozpinar
- Department of Medical Biochemistry, Acibadem University, Istanbul, Turkey
| | - M Emin Ozcan
- Department of Neurology, Kizilay Hospital, Bakirkoy, Istanbul, Turkey
| | | | - Ilhan Elmaci
- Neuroacademy Research Group, Istanbul, Turkey; Department of Neurosurgery, Memorial Hospital, Istanbul, Turkey
| |
Collapse
|
|
31
|
van Westrhenen A, Smidt LCA, Seute T, Nierkens S, Stork ACJ, Minnema MC, Snijders TJ. Diagnostic markers for CNS lymphoma in blood and cerebrospinal fluid: a systematic review. Br J Haematol 2018; 182:384-403. [PMID: 29808930 PMCID: PMC6099264 DOI: 10.1111/bjh.15410] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Accepted: 03/28/2018] [Indexed: 12/31/2022]
Abstract
Diagnosing central nervous system (CNS) lymphoma remains a challenge. Most patients have to undergo brain biopsy to obtain tissue for diagnosis, with associated risks of serious complications. Diagnostic markers in blood or cerebrospinal fluid (CSF) could facilitate early diagnosis with low complication rates. We performed a systematic literature search for studies on markers in blood or cerebrospinal fluid for the diagnosis CNS lymphoma and assessed the methodological quality of studies with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS‐2). We evaluated diagnostic value of the markers at a given threshold, as well as differences between mean or median levels in patients versus control groups. Twenty‐five studies were included, reporting diagnostic value for 18 markers in CSF (microRNAs ‐21, ‐19b, and ‐92a, RNU2‐1f, CXCL13, interleukins ‐6, ‐8, and ‐10, soluble interleukin‐2‐receptor, soluble CD19, soluble CD27, tumour necrosis factor‐alfa, beta‐2‐microglobulin, antithrombin III, soluble transmembrane activator and calcium modulator and cyclophilin ligand interactor, soluble B cell maturation antigen, neopterin and osteopontin) and three markers in blood (microRNA‐21 soluble CD27, and beta‐2‐microglobulin). All studies were at considerable risk of bias and there were concerns regarding the applicability of 15 studies. CXCL‐13, beta‐2‐microglobulin and neopterin have the highest potential in diagnosing CNS lymphoma, but further study is still needed before they can be used in clinical practice.
Collapse
Affiliation(s)
- Anouk van Westrhenen
- University Medical Center Utrecht, Utrecht, The Netherlands.,Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands
| | | | - Tatjana Seute
- University Medical Center Utrecht, Utrecht, The Netherlands.,Department of Neurology & Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Stefan Nierkens
- University Medical Center Utrecht, Utrecht, The Netherlands.,Laboratory of Translational Immunology, Department Laboratory and Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Abraham C J Stork
- University Medical Center Utrecht, Utrecht, The Netherlands.,Department of Neurology & Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.,Department of Neurology, General Hospital Hietzing with Neurological Center Rosenhügel, Vienna, Austria
| | - Monique C Minnema
- University Medical Center Utrecht, Utrecht, The Netherlands.,Department of Haematology, Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Tom J Snijders
- University Medical Center Utrecht, Utrecht, The Netherlands.,Department of Neurology & Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
| |
Collapse
|
|
32
|
Wick A, Kessler T, Elia AEH, Winkler F, Batchelor TT, Platten M, Wick W. Glioblastoma in elderly patients: solid conclusions built on shifting sand? Neuro Oncol 2018; 20:174-183. [PMID: 29016815 PMCID: PMC5777484 DOI: 10.1093/neuonc/nox133] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Management of glioblastoma in the elderly population is challenging. In the near future, more than half of patients with this tumor will be over the age of 65. Clinicians have been historically reluctant to treat such patients with the same intensity as younger patients. Due to upper age limits or poor accrual of elderly patients in clinical trials, randomized data for this patient population have been relatively sparse until recently. In this review, we will discuss the concept of an elderly patient population, describe evidence for molecular differences in glioblastoma of elderly versus young patients, evaluate recent first-line trials studying glioblastoma in elderly patients, and discuss best therapeutic practices including the value of molecular testing.
Collapse
Affiliation(s)
- Antje Wick
- Neurology Clinic & German Consortium for Translational Cancer Research (DKTK), Heidelberg University Medical Center & DKFZ, Heidelberg, Germany
| | - Tobias Kessler
- Neurology Clinic & German Consortium for Translational Cancer Research (DKTK), Heidelberg University Medical Center & DKFZ, Heidelberg, Germany
| | - Andrew E H Elia
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Frank Winkler
- Neurology Clinic & German Consortium for Translational Cancer Research (DKTK), Heidelberg University Medical Center & DKFZ, Heidelberg, Germany
| | - Tracy T Batchelor
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | | | - Wolfgang Wick
- Neurology Clinic & German Consortium for Translational Cancer Research (DKTK), Heidelberg University Medical Center & DKFZ, Heidelberg, Germany
| |
Collapse
|
|
33
|
Zhan R, Xia L, Shao J, Wang C, Chen D. Polysaccharide isolated from Chinese jujube fruit (Zizyphus jujuba cv. Junzao) exerts anti-inflammatory effects through MAPK signaling. J Funct Foods 2018. [DOI: 10.1016/j.jff.2017.11.026] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
|
|
34
|
A Dexamethasone-regulated Gene Signature Is Prognostic for Poor Survival in Glioblastoma Patients. J Neurosurg Anesthesiol 2017; 29:46-58. [PMID: 27653222 DOI: 10.1097/ana.0000000000000368] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Dexamethasone is reported to induce both tumor-suppressive and tumor-promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. METHODS We utilized 3 independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in The Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data databases. In silico Connectivity Map analysis identified camptothecin as antagonist to dexamethasone-induced negative effects. RESULTS Pathway analyses predicted an activation of dexamethasone network (z-score: 2.908). Top activated canonical pathways included "role of breast cancer 1 in DNA damage response" (P=1.07E-04). GSCs were protected against temozolomide-induced apoptosis when coincubated with dexamethasone. Altered cellular functions included cell movement, cell survival, and apoptosis with z-scores of 2.815, 5.137, and -3.122, respectively. CCAAT/enhancer binding protein beta (CEBPB) was activated in a dose dependent manner specifically in slow-dividing "stem-like" cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk scores had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone-induced oncogenic effects. CONCLUSIONS Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value in patients. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects.
Collapse
|
|
35
|
Role of ketogenic metabolic therapy in malignant glioma: A systematic review. Crit Rev Oncol Hematol 2017; 112:41-58. [DOI: 10.1016/j.critrevonc.2017.02.016] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2016] [Revised: 01/30/2017] [Accepted: 02/14/2017] [Indexed: 12/22/2022] Open
|
|
36
|
Piazza M, Munasinghe J, Murayi R, Edwards N, Montgomery B, Walbridge S, Merrill M, Chittiboina P. Simulating vasogenic brain edema using chronic VEGF infusion. J Neurosurg 2017; 127:905-916. [PMID: 28059647 DOI: 10.3171/2016.9.jns1627] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVE To study peritumoral brain edema (PTBE), it is necessary to create a model that accurately simulates vasogenic brain edema (VBE) without introducing a complicated tumor environment. PTBE associated with brain tumors is predominantly a result of vascular endothelial growth factor (VEGF) secreted by brain tumors, and VEGF infusion alone can lead to histological blood-brain barrier (BBB) breakdown in the absence of tumor. VBE is intimately linked to BBB breakdown. The authors sought to establish a model for VBE with chronic infusion of VEGF that can be validated by serial in-vivo MRI and histological findings. METHODS Male Fischer rats (n = 182) underwent stereotactic striatal implantation of MRI-safe brain cannulas for chronic infusion of VEGF (2-20 µg/ml). Following a preinfusion phase (4-6 days), the rats were exposed to VEGF or control rat serum albumin (1.5 µl/hr) for as long as 144 hours. Serial MRI was performed during infusion on a high-field (9.4-T) machine at 12-24, 24-36, 48-72, and 120-144 hours. Rat brains were then collected and histological analysis was performed. RESULTS Control animals and animals infused with 2 µg/ml of VEGF experienced no neurological deficits, seizure activity, or abnormal behavior. Animals treated with VEGF demonstrated a significantly larger volume (42.90 ± 3.842 mm3) of T2 hyper-attenuation at 144 hours when compared with the volume (8.585 ± 1.664 mm3) in control animals (mean difference 34.31 ± 4.187 mm3, p < 0.0001, 95% CI 25.74-42.89 mm3). Postcontrast T1 enhancement in the juxtacanalicular region indicating BBB breakdown was observed in rats undergoing infusion with VEGF. At the later time periods (120-144 hrs) the volume of T1 enhancement (34.97 ± 8.99 mm3) was significantly less compared with the region of edema (p < 0.0001). Histologically, no evidence of necrosis or inflammation was observed with VEGF or control infusion. Immunohistochemical analysis demonstrated astrocyte activation, vascular remodeling, and increased claudin-5 expression in juxtacanalicular regions. Aquaporin-4 expression was increased in both control and VEGF animals in the juxtacanalicular regions. CONCLUSIONS The results of this study show that chronic brain infusion of VEGF creates a reliable model of VBE. This model lacks necrosis and inflammation that are characteristic of previous models of VBE. The model allows for a precise investigation into the mechanism of VBE formation. The authors also anticipate that this model will allow for investigation into the mechanism of glucocorticoid action in abrogating VBE, and to test novel therapeutic strategies targeting PTBE.
Collapse
Affiliation(s)
- Martin Piazza
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, and
| | | | - Roger Murayi
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, and
| | - Nancy Edwards
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, and
| | - Blake Montgomery
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, and
| | - Stuart Walbridge
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, and
| | - Marsha Merrill
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, and
| | - Prashant Chittiboina
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, and
| |
Collapse
|
|
37
|
Catford S, Wang YY, Wong R. Pituitary stalk lesions: systematic review and clinical guidance. Clin Endocrinol (Oxf) 2016; 85:507-21. [PMID: 26950774 DOI: 10.1111/cen.13058] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Revised: 03/01/2016] [Accepted: 03/04/2016] [Indexed: 12/15/2022]
Abstract
The spectrum of pituitary stalk (PS) pathology is vast, presenting a diagnostic challenge. Published large series of PS lesions demonstrate neoplastic conditions are most frequent, followed by inflammatory, infectious and congenital diseases. Inflammatory pathologies however, account for the majority of PS lesions in published small case series and case reports. Physicians must be familiar with the major differential diagnoses and necessary investigations. A comprehensive history and thorough clinical examination is critical. Although magnetic resonance imaging of the PS in disease is nonspecific, associated intracranial features may narrow the differential diagnosis. Initial investigations include basic pathology and computer tomography imaging of the neck, chest, abdomen and pelvis. Further investigations should be guided by the clinical context. PS biopsy should be considered when a diagnosis is regarded essential in centres where an experienced neurosurgeon is available. Treatment is dependent on the underlying disease process and may necessitate pituitary hormone replacement.
Collapse
Affiliation(s)
- Sarah Catford
- Department of Endocrinology and Diabetes, Western Health, Melbourne, Vic., Australia.
| | - Yi Yuen Wang
- Department of Neurosurgery and Surgery, The University of Melbourne, St Vincent's Hospital, Melbourne, Vic., Australia
| | - Rosemary Wong
- Department of Endocrinology and Diabetes, Western Health, Melbourne, Vic., Australia
| |
Collapse
|
|
38
|
|
|
39
|
Choi IY, Piccio L, Childress P, Bollman B, Ghosh A, Brandhorst S, Suarez J, Michalsen A, Cross AH, Morgan TE, Wei M, Paul F, Bock M, Longo VD. A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms. Cell Rep 2016; 15:2136-2146. [PMID: 27239035 DOI: 10.1016/j.celrep.2016.05.009] [Citation(s) in RCA: 348] [Impact Index Per Article: 38.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Revised: 02/20/2016] [Accepted: 04/26/2016] [Indexed: 01/20/2023] Open
Abstract
Dietary interventions have not been effective in the treatment of multiple sclerosis (MS). Here, we show that periodic 3-day cycles of a fasting mimicking diet (FMD) are effective in ameliorating demyelination and symptoms in a murine experimental autoimmune encephalomyelitis (EAE) model. The FMD reduced clinical severity in all mice and completely reversed symptoms in 20% of animals. These improvements were associated with increased corticosterone levels and regulatory T (Treg) cell numbers and reduced levels of pro-inflammatory cytokines, TH1 and TH17 cells, and antigen-presenting cells (APCs). Moreover, the FMD promoted oligodendrocyte precursor cell regeneration and remyelination in axons in both EAE and cuprizone MS models, supporting its effects on both suppression of autoimmunity and remyelination. We also report preliminary data suggesting that an FMD or a chronic ketogenic diet are safe, feasible, and potentially effective in the treatment of relapsing-remitting multiple sclerosis (RRMS) patients (NCT01538355).
Collapse
Affiliation(s)
- In Young Choi
- Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
| | - Laura Piccio
- Department of Neurology and Neurosurgery and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Patra Childress
- Global Medicine Program, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
| | - Bryan Bollman
- Department of Neurology and Neurosurgery and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Arko Ghosh
- Department of Neuroscience, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA
| | - Sebastian Brandhorst
- Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
| | - Jorge Suarez
- Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
| | - Andreas Michalsen
- Institute of Social Medicine, Epidemiology and Health Economics, Charité University Medicine Berlin, 10117 Berlin, Germany
| | - Anne H Cross
- Department of Neurology and Neurosurgery and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Todd E Morgan
- Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
| | - Min Wei
- Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
| | - Friedemann Paul
- NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine Berlin, 10117 Berlin, Germany; Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, 10117 Berlin, Germany
| | - Markus Bock
- NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine Berlin, 10117 Berlin, Germany; Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, 10117 Berlin, Germany
| | - Valter D Longo
- Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA; Department of Neuroscience, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; IFOM, FIRC Institute of Molecular Oncology, 20139 Milan, Italy.
| |
Collapse
|
|
40
|
Schwarzrock C. Collaboration in the presence of cerebral edema: The complications of steroids. Surg Neurol Int 2016; 7:S185-9. [PMID: 27114853 PMCID: PMC4825348 DOI: 10.4103/2152-7806.179228] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2015] [Accepted: 02/09/2016] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND Brain tumor patients often present with neurological changes in the presence of cerebral edema. High-dose dexamethasone is often required for symptom management in brain tumor patients. There are limitations in the foundational research that support the recommendations for appropriate prescribing of dexamethasone. Understanding these limitations can help prescribers and care teams collaborate to better manage this unique patient population as well as identify areas for further research. METHODS Evidence-based clinical practice guidelines for the management of adult brain tumor patients were reviewed from several certifying organizations. A complex database search and literature review was completed regarding relevant evidence used within these guidelines and for any supporting literature. The search was limited to MEDLINE, Cumulative Index to Nursing and Allied Health, Cochrane Library, and the National Guideline Clearinghouse using keywords. Each selected evidence-based guideline underwent appraisal using the Johns Hopkins Evidence-based Practice Model. RESULTS All clinical practice guidelines identified recommendations for appropriate dosing and tapering of dexamethasone. The management of steroid-induced side effects was addressed in two of the reviewed guidelines. Only one guideline identified specific nursing interventions for monitoring steroid-related side effects. No guideline addressed interval timing of provider or nursing-based interventions as well as the role of collaboration between provider and nurse in monitoring for steroid toxicities. CONCLUSIONS More high-quality, well-controlled studies are needed around dexamethasone dosing for the management of cerebral edema. Clinical practice guidelines need to encompass both the prescriber and nursing-based interventions. Collaboration between disciplines is a necessity when monitoring and managing steroid-induced toxicities in brain tumor patients. Future evidence-based guidelines need recommendations for appropriate interval screening tests and quantifiable tools needed to aid in monitoring steroid-induced complications.
Collapse
Affiliation(s)
- Camille Schwarzrock
- John Nasseff Neuroscience Specialty Clinic, Part of Allina Health, 225 North Smith Avenue, Suite 500, St. Paul, MN 55102, USA
| |
Collapse
|
|
41
|
Berger MS, Hervey-Jumper S, Wick W. Astrocytic gliomas WHO grades II and III. HANDBOOK OF CLINICAL NEUROLOGY 2016; 134:345-60. [PMID: 26948365 DOI: 10.1016/b978-0-12-802997-8.00021-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
World Health Organization grades II and III lower-grade astrocytomas are a challenging area in neuro-oncology. One the one hand, for proper diagnosis, the analysis of molecular factors, especially mutation status of isocitrate dehydrogenase and 1p/19q status in the tumor status needs to be done in addition to classical neuropathology. Further, the high clinical and prognostic value of a maximal safe resection requires a profound knowledge of presurgical diagnosis and surgical as well as imaging techniques to ensure optimal outcome for patients. Also medical treatment may be more intensive than previously believed, with randomized trials providing evidence for a benefit in overall survival by combined chemoradiation versus radiation alone. A critical problem concerns the considerable undesirable effects of therapeutic interventions on long-term health-related quality of life, cognitive and functional outcome as well as future developments in this still difficult disease that will need to be addressed in future trials.
Collapse
Affiliation(s)
- Mitchel S Berger
- Department of Neurological Surgery, University of California, San Francisco, CA, USA.
| | - Shawn Hervey-Jumper
- Department of Neurological Surgery, Taubman Health Center, Ann Arbor, MI, USA
| | - Wolfgang Wick
- Department of Neurooncology, University Clinic of Heidelberg, Heidelberg, Germany
| |
Collapse
|
|
42
|
Esquenazi Y, Lo VP, Lee K. Critical Care Management of Cerebral Edema in Brain Tumors. J Intensive Care Med 2015; 32:15-24. [PMID: 26647408 DOI: 10.1177/0885066615619618] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 10/05/2015] [Accepted: 11/06/2015] [Indexed: 12/21/2022]
Abstract
Cerebral edema associated with brain tumors is extremely common and can occur in both primary and metastatic tumors. The edema surrounding brain tumors results from leakage of plasma across the vessel wall into the parenchyma secondary to disruption of the blood-brain barrier. The clinical signs of brain tumor edema depend on the location of the tumor as well as the extent of the edema, which often exceeds the mass effect induced by the tumor itself. Uncontrolled cerebral edema may result in increased intracranial pressure and acute herniation syndromes that can result in permanent neurological dysfunction and potentially fatal herniation. Treatment strategies for elevated intracranial pressure consist of general measures, medical interventions, and surgery. Alhough the definitive treatment for the edema may ultimately be surgical resection of the tumor, the impact of the critical care management cannot be underestimated and thus patients must be vigilantly monitored in the intensive care unit. In this review, we discuss the pathology, pathophysiology, and clinical features of patients presenting with cerebral edema. Imaging findings and treatment modalities used in the intensive care unit are also discussed.
Collapse
Affiliation(s)
- Yoshua Esquenazi
- Vivian L. Smith Department of Neurosurgery, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Victor P Lo
- Vivian L. Smith Department of Neurosurgery, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Kiwon Lee
- Vivian L. Smith Department of Neurosurgery, University of Texas Health Science Center at Houston, Houston, TX, USA
| |
Collapse
|
|
43
|
Siasios I, Fotiadou A, Fotakopoulos G, Ioannou M, Anagnostopoulos V, Fountas K. Primary Diffuse Large B-Cell Lymphoma of Central Nervous System: Is Still Surgery an Unorthodox Treatment? J Clin Med Res 2015; 7:1007-12. [PMID: 26566417 PMCID: PMC4625808 DOI: 10.14740/jocmr2376w] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/14/2015] [Indexed: 01/08/2023] Open
Abstract
Primary central nervous system lymphoma (PCNSL) is characterized as an extra-nodal non-Hodgkin lymphoma which develops from the neuraxis. The purpose was to report a case of a patient with a supra-tentorial tumor who underwent subtotal resection of his tumor as his biopsy was not indicative of a PCNSL tumor and had uneventful recovery until his last follow-up. A 42-year-old man was admitted to our department for generalized epileptic seizures. CT and MRI examinations revealed a tumor in his right parietal-occipital lobe that was surrounded by edema and was enhancing after gadolinium administration. The patient underwent a navigation-assisted parieto-occipital craniotomy and posterior parietal transcortical approach for tumor biopsy which was not indicative of PCNSL tumor. The surgical team decided to remove the tumor on site. Histological analysis of the resected specimen showed primary diffuse large B-cell lymphoma. Combined chemotherapy and radiation therapy was applied to the patient, and at his last follow-up (16 months), he is tumor free. In our case as in several other studies during the last decade, the outcome after the surgical resection of a PCNSL tumor in combination to radiation and chemotherapy was unexpectedly good. The role of surgery probably should be reconsidered for single lesion PCNSL tumors.
Collapse
Affiliation(s)
- Ioannis Siasios
- Department of Neurosurgery, University Hospital of Larissa, Mezourlo 1, Larissa 41110, Greece
| | - Aggeliki Fotiadou
- Department of Neurosurgery, University Hospital of Larissa, Mezourlo 1, Larissa 41110, Greece
| | - George Fotakopoulos
- Department of Neurosurgery, University Hospital of Larissa, Mezourlo 1, Larissa 41110, Greece
| | - Maria Ioannou
- Department of Pathology, University Hospital of Larissa, Mezourlo 1, Larissa 41110, Greece
| | | | - Konstantinos Fountas
- Department of Neurosurgery, University Hospital of Larissa, Mezourlo 1, Larissa 41110, Greece
| |
Collapse
|
|
44
|
Rutledge MR, Waddell JA, Solimando DA. Bevacizumab and Temozolomide Plus Radiation Regimen for Glioblastoma Multiforme. Hosp Pharm 2015; 50:672-7. [PMID: 26823616 PMCID: PMC4686471 DOI: 10.1310/hpj5008-672] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.
Collapse
Affiliation(s)
- Matthew R Rutledge
- Chief, Hematology-Oncology Pharmacy Service, Department of Pharmacy, Madigan Army Medical Center , Tacoma, Washington . The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the US Department of the Army or the Department of Defense
| | - J Aubrey Waddell
- Chief, Hematology-Oncology Pharmacy Service, Department of Pharmacy, Madigan Army Medical Center , Tacoma, Washington . The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the US Department of the Army or the Department of Defense
| | - Dominic A Solimando
- Chief, Hematology-Oncology Pharmacy Service, Department of Pharmacy, Madigan Army Medical Center , Tacoma, Washington . The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the US Department of the Army or the Department of Defense
| |
Collapse
|
|
45
|
Abstract
OBJECTIVE The purpose of this article is to provide a comprehensive imaging review of the common hormonal therapies used in oncology and the side effects associated with them. CONCLUSION Commonly used hormones in oncology include corticosteroids, somatostatin analogues, progestins, gonadotropin-releasing hormone agonists and antagonists, antiandrogens, aromatase inhibitors, and selective estrogen receptor modulators. Familiarity with these hormones and their side effects can help radiologists to be vigilant for the side effects and complications of these agents.
Collapse
|
|
46
|
Weller M, Wick W, Aldape K, Brada M, Berger M, Pfister SM, Nishikawa R, Rosenthal M, Wen PY, Stupp R, Reifenberger G. Glioma. Nat Rev Dis Primers 2015; 1:15017. [PMID: 27188790 DOI: 10.1038/nrdp.2015.17] [Citation(s) in RCA: 746] [Impact Index Per Article: 74.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Gliomas are primary brain tumours that are thought to derive from neuroglial stem or progenitor cells. On the basis of their histological appearance, they have been traditionally classified as astrocytic, oligodendroglial or ependymal tumours and assigned WHO grades I-IV, which indicate different degrees of malignancy. Tremendous progress in genomic, transcriptomic and epigenetic profiling has resulted in new concepts of classifying and treating gliomas. Diffusely infiltrating gliomas in adults are now separated into three overarching tumour groups with distinct natural histories, responses to treatment and outcomes: isocitrate dehydrogenase (IDH)-mutant, 1p/19q co-deleted tumours with mostly oligodendroglial morphology that are associated with the best prognosis; IDH-mutant, 1p/19q non-co-deleted tumours with mostly astrocytic histology that are associated with intermediate outcome; and IDH wild-type, mostly higher WHO grade (III or IV) tumours that are associated with poor prognosis. Gliomas in children are molecularly distinct from those in adults, the majority being WHO grade I pilocytic astrocytomas characterized by circumscribed growth, favourable prognosis and frequent BRAF gene fusions or mutations. Ependymal tumours can be molecularly subdivided into distinct epigenetic subgroups according to location and prognosis. Although surgery, radiotherapy and alkylating agent chemotherapy are still the mainstay of treatment, individually tailored strategies based on tumour-intrinsic dominant signalling pathways and antigenic tumour profiles may ultimately improve outcome. For an illustrated summary of this Primer, visit: http://go.nature.com/TXY7Ri.
Collapse
Affiliation(s)
- Michael Weller
- Department of Neurology and Brain Tumor Center, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 26, CH-8091 Zurich, Switzerland
| | - Wolfgang Wick
- Neurology Clinic, University of Heidelberg and German Cancer Research Center, Heidelberg, Germany
| | - Ken Aldape
- Department of Pathology, University Health Network, Toronto, Ontario, Canada
| | - Michael Brada
- Department of Molecular and Clinical Cancer Medicine and Department of Radiation Oncology, University of Liverpool and Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK
| | - Mitchell Berger
- Department of Neurological Surgery and Brain Tumor Research Center, University of California, San Francisco, California, USA
| | - Stefan M Pfister
- Division of Pediatric Neuro-Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Pediatric Haematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany
| | - Ryo Nishikawa
- Department of Neuro-Oncology and Neurosurgery, Saitama Medical University, Saitama, Japan
| | - Mark Rosenthal
- Department of Medical Oncology, The Royal Melbourne Hospital, Victoria 3050, Australia
| | - Patrick Y Wen
- Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts, USA
| | - Roger Stupp
- Department of Oncology and Brain Tumor Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Guido Reifenberger
- Department of Neuropathology, Heinrich Heine University Düsseldorf, and German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Heidelberg, partner site Essen/Düsseldorf, Germany
| |
Collapse
|
|
47
|
Mukherjee S, Thakur B, Corns R, Connor S, Bhangoo R, Ashkan K, Gullan R. Resection of olfactory groove meningioma - a review of complications and prognostic factors. Br J Neurosurg 2015; 29:685-92. [PMID: 26174632 DOI: 10.3109/02688697.2015.1054348] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
INTRODUCTION High complication rates have been cited following olfactory groove meningioma (OGM) resection but data are lacking on attendant risk factors. We aimed to review the complications following OGM resection and identify prognostic factors. METHODS A retrospective review was performed on 34 consecutive patients who underwent primary OGM resection at a single London institution between March 2008 and February 2013. Collected data included patient comorbidities, pre-operative corticosteroid use, tumour characteristics, imaging features, operative details, extent of resection, histology, use of elective post-operative ventilation, complications, recurrence and mortality. RESULTS Complication rate was 39%. 58% of complications required intensive care or re-operation. Higher complication rates occurred with OGM > 40 mm diameter versus ≤ 40 mm (53 vs. 28%; p = 0.16); OGM with versus without severe perilesional oedema (59 vs. 19%; p = 0.26), more evident when corrected for tumour size; and patients receiving 1-2 days versus 3-5 days of pre-operative dexamethasone (75 vs. 19%; p = 0.016). Patients who were electively ventilated post-operatively versus those who were not had higher risk tumours but a lower complication rate (17 vs. 44%; p = 0.36) and a higher proportion making a good recovery (83 vs. 55%; p = 0.20). Complete versus incomplete resection had a higher complication rate (50 vs. 23%; p = 0.16) but no recurrence (0 vs. 25%; p = 0.07). CONCLUSION Risk of morbidity with OGM resection is high. Higher complication risk is associated with larger tumours and greater perilesional oedema. Pre-operative dexamethasone for 3-5 days versus shorter periods may reduce the risk of complications. We describe a characteristic pattern of perilesional oedema termed 'sabre-tooth' sign, whose presence is associated with a higher complication rate and may represent an important radiological prognostic sign. Elective post-operative ventilation for patients with high-risk tumours may reduce the risk of complications.
Collapse
Affiliation(s)
- Soumya Mukherjee
- a Department of Neurosurgery , King's College Hospital , London , UK
| | - Bhaskar Thakur
- a Department of Neurosurgery , King's College Hospital , London , UK
| | - Robert Corns
- a Department of Neurosurgery , King's College Hospital , London , UK
| | - Steve Connor
- a Department of Neurosurgery , King's College Hospital , London , UK
| | - Ranjeev Bhangoo
- a Department of Neurosurgery , King's College Hospital , London , UK
| | - Keyoumars Ashkan
- a Department of Neurosurgery , King's College Hospital , London , UK
| | - Richard Gullan
- a Department of Neurosurgery , King's College Hospital , London , UK
| |
Collapse
|
|
48
|
Managing Disease and Therapy-Related Complications in Patients with Central Nervous System Tumors. Curr Treat Options Oncol 2015; 16:38. [DOI: 10.1007/s11864-015-0357-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
|
|
49
|
Alan N, Seicean A, Seicean S, Neuhauser D, Benzel EC, Weil RJ. Preoperative steroid use and the incidence of perioperative complications in patients undergoing craniotomy for definitive resection of a malignant brain tumor. J Clin Neurosci 2015; 22:1413-9. [PMID: 26073371 DOI: 10.1016/j.jocn.2015.03.009] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Accepted: 03/21/2015] [Indexed: 12/21/2022]
Abstract
We studied the impact of preoperative steroids on 30 day morbidity and mortality of craniotomy for definitive resection of malignant brain tumors. Glucocorticoids are used to treat peritumoral edema in patients with malignant brain tumors, however, prolonged (⩾ 10 days) use of preoperative steroids as a risk factor for perioperative complications following resection of brain tumors has not been studied comprehensively. Therefore, we identified 4407 patients who underwent craniotomy to resect a malignant brain tumor between 2007 and 2012, who were reported in the National Surgical Quality Improvement Program, a prospectively collected clinical database. Metastatic brain tumors constituted 37.5% (n=1611) and primary malignant gliomas 62.5% (n=2796) of the study population. We used logistic regression to assess the association between preoperative steroid use and perioperative complications before and after 1:1 propensity score matching. Patients who received steroids constituted 22.8% of the population (n=1009). In the unmatched cohort, steroid use was associated with decreased length of hospitalization (odds ratio [OR] 0.7; 95% confidence interval [CI] 0.6-0.8), however, the risk for readmission (OR 1.5; 95% CI 1.2-1.8) was increased. In the propensity score matched cohort (n=465), steroid use was not statistically associated with any adverse outcomes. Patients who received steroids were less likely to stay hospitalized for a protracted period of time, but were more likely to be readmitted after discharge following craniotomy. As an independent risk factor, preoperative steroid use was not associated with any observed perioperative complications. The findings of this study suggest that preoperative steroids do not independently compromise the short term outcome of craniotomy for resection of malignant brain tumors.
Collapse
Affiliation(s)
- Nima Alan
- School of Medicine, Case Western Reserve University, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
| | - Andreea Seicean
- School of Medicine, Case Western Reserve University, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA
| | - Sinziana Seicean
- Department of Pulmonary, Critical Care and Sleep Medicine, University Hospitals, Cleveland, OH, USA; Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Duncan Neuhauser
- Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA
| | - Edward C Benzel
- Department of Neurosurgery, The Neurological Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Robert J Weil
- The Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Department of Neurosurgery, The Neurological Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Neurosurgery, Geisinger Health System, Danville, PA, USA
| |
Collapse
|
|
50
|
Incidence, risk factors, and reasons for hospitalization among glioblastoma patients receiving chemoradiation. J Neurooncol 2015; 124:137-46. [PMID: 26033544 DOI: 10.1007/s11060-015-1820-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Accepted: 05/22/2015] [Indexed: 12/21/2022]
Abstract
Despite a high symptom burden, little is known about the incidence or predictors of hospitalization among glioblastoma patients, including risks during chemoradiation (CRT). We studied 196 consecutive newly diagnosed glioblastoma patients treated at our institution from 2006-2010. Toxicity data were reviewed during and after the CRT phase, defined as the period between diagnosis and 6 weeks after radiotherapy completion. Logistic regression and proportional hazards modeling identified predictors of hospitalization and overall survival (OS). Median age was 59 years (range, 23-90) and 83 % had Karnofsky performance status (KPS) score ≥ 70. Twenty-six percent of patients underwent gross total resection, 77 % received ≥ 59.4 Gy of radiotherapy, and 89 % received concurrent temozolomide. Median OS was 15.6 months (IQR, 8.5-26.8 months). Forty-three percent of patients were hospitalized during the CRT phase; OS was 10.7 vs. 17.8 months for patients who were vs. were not hospitalized, respectively (P < .001). Nearly half of the hospitalizations were due to generalized weakness (17 % of hospitalizations), seizures (16 %), or venous thromboembolism (13 %). On multivariate analysis, age (odds ratio [OR], 1.03; 95 % CI, 1.002-1.060; P = .034) and KPS (OR, 0.95; 95 % CI, 0.93-0.97; P < .001) were associated with risk of hospitalization. Hospitalization during the CRT phase was associated with decreased OS (adjusted hazard ratio, 1.47; 95 % CI, 1.01-2.13; P = .043), after adjustment for known prognostic factors. Hospitalization during the CRT phase is common among glioblastoma patients in the temozolomide era and is associated with shorter overall survival.
Collapse
|