| 1. |
- Peden, Carol J., et al.
(författare)
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Enhanced Recovery After Surgery (ERAS®) Society Consensus Guidelines for Emergency Laparotomy Part 3 : Organizational Aspects and General Considerations for Management of the Emergency Laparotomy Patient
- 2023
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Ingår i: World Journal of Surgery. - : Springer. - 0364-2313 .- 1432-2323. ; 47:8, s. 1881-1898
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: This is Part 3 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy using an enhanced recovery after surgery (ERAS) approach. This paper addresses organizational aspects of care.METHODS: Experts in management of the high-risk and emergency general surgical patient were invited to contribute by the International ERAS® Society. PubMed, Cochrane, Embase, and MEDLINE database searches were performed for ERAS elements and relevant specific topics. Studies were selected with particular attention to randomized clinical trials, systematic reviews, meta-analyses and large cohort studies, and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations.RESULTS: Components of organizational aspects of care were considered. Consensus was reached after three rounds of a modified Delphi process.CONCLUSIONS: These guidelines are based on best current available evidence for organizational aspects of an ERAS® approach to patients undergoing emergency laparotomy and include discussion of less common aspects of care for the surgical patient, including end-of-life issues. These guidelines are not exhaustive but pull together evidence on important components of care for this high-risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies.
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| 2. |
- Peden, Carol J., et al.
(författare)
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Guidelines for Perioperative Care for Emergency Laparotomy Enhanced Recovery After Surgery (ERAS) Society Recommendations : Part 1-Preoperative: Diagnosis, Rapid Assessment and Optimization
- 2021
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Ingår i: World Journal of Surgery. - : Springer. - 0364-2313 .- 1432-2323. ; 45, s. 1272-1290
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Enhanced Recovery After Surgery (ERAS) protocols reduce length of stay, complications and costs for a large number of elective surgical procedures. A similar, structured approach appears to improve outcomes, including mortality, for patients undergoing high-risk emergency general surgery, and specifically emergency laparotomy. These are the first consensus guidelines for optimal care of these patients using an ERAS approach.METHODS: Experts in aspects of management of the high-risk and emergency general surgical patient were invited to contribute by the International ERAS® Society. Pubmed, Cochrane, Embase, and MEDLINE database searches on English language publications were performed for ERAS elements and relevant specific topics. Studies on each item were selected with particular attention to randomized controlled trials, systematic reviews, meta-analyses and large cohort studies, and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Recommendations were made on the best level of evidence, or extrapolation from studies on non-emergency patients when appropriate. The Delphi method was used to validate final recommendations. The guideline has been divided into two parts: Part 1-Preoperative Care and Part 2-Intraoperative and Postoperative management. This paper provides guidelines for Part 1.RESULTS: Twelve components of preoperative care were considered. Consensus was reached after three rounds.CONCLUSIONS: These guidelines are based on the best available evidence for an ERAS approach to patients undergoing emergency laparotomy. Initial management is particularly important for patients with sepsis and physiological derangement. These guidelines should be used to improve outcomes for these high-risk patients.
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| 3. |
- Scott, Michael J., et al.
(författare)
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Consensus Guidelines for Perioperative Care for Emergency Laparotomy Enhanced Recovery After Surgery (ERAS®) Society Recommendations Part 2-Emergency Laparotomy : Intra- and Postoperative Care
- 2023
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Ingår i: World Journal of Surgery. - : Springer. - 0364-2313 .- 1432-2323. ; 47:8, s. 1850-1880
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: This is Part 2 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy (EL) using an Enhanced Recovery After Surgery (ERAS) approach. This paper addresses intra- and postoperative aspects of care.METHODS: Experts in aspects of management of high-risk and emergency general surgical patients were invited to contribute by the International ERAS® Society. PubMed, Cochrane, Embase, and Medline database searches were performed for ERAS elements and relevant specific topics. Studies on each item were selected with particular attention to randomized clinical trials, systematic reviews, meta-analyses, and large cohort studies and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations. Some ERAS® components covered in other guideline papers are outlined only briefly, with the bulk of the text focusing on key areas pertaining specifically to EL.RESULTS: Twenty-three components of intraoperative and postoperative care were defined. Consensus was reached after three rounds of a modified Delphi Process.CONCLUSIONS: These guidelines are based on best available evidence for an ERAS® approach to patients undergoing EL. These guidelines are not exhaustive but pull together evidence on important components of care for this high-risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies.
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| 4. |
- Weller, Michael, et al.
(författare)
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EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood.
- 2021
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Ingår i: Nature reviews. Clinical oncology. - : Springer Science and Business Media LLC. - 1759-4782 .- 1759-4774. ; 18, s. 170-186
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Forskningsöversikt (refereegranskat)abstract
- In response to major changes in diagnostic algorithms and the publication of mature results from various large clinical trials, the European Association of Neuro-Oncology (EANO) recognized the need to provide updated guidelines for the diagnosis and management of adult patients with diffuse gliomas. Through these evidence-based guidelines, a task force of EANO provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. The diagnostic component is based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System and the subsequent recommendations of the Consortium to Inform Molecular and Practical Approaches to CNS Tumour Taxonomy - Not Officially WHO (cIMPACT-NOW). With regard to therapy, we formulated recommendations based on the results from the latest practice-changing clinical trials and also provide guidance for neuropathological and neuroradiological assessment. In these guidelines, we define the role of the major treatment modalities of surgery, radiotherapy and systemic pharmacotherapy, covering current advances and cognizant that unnecessary interventions and expenses should be avoided. This document is intended to be a source of reference for professionals involved in the management of adult patients with diffuse gliomas, for patients and caregivers, and for health-care providers.
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| 5. |
- Ali, Zaheer, et al.
(författare)
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Zebrafish patient-derived xenograft models predict lymph node involvement and treatment outcome in non-small cell lung cancer
- 2022
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Ingår i: Journal of Experimental & Clinical Cancer Research. - : BMC. - 1756-9966. ; 41:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Accurate predictions of tumor dissemination risks and medical treatment outcomes are critical to personalize therapy. Patient-derived xenograft (PDX) models in mice have demonstrated high accuracy in predicting therapeutic outcomes, but methods for predicting tumor invasiveness and early stages of vascular/lymphatic dissemination are still lacking. Here we show that a zebrafish tumor xenograft (ZTX) platform based on implantation of PDX tissue fragments recapitulate both treatment outcome and tumor invasiveness/dissemination in patients, within an assay time of only 3 days. Methods Using a panel of 39 non-small cell lung cancer PDX models, we developed a combined mouse-zebrafish PDX platform based on direct implantation of cryopreserved PDX tissue fragments into zebrafish embryos, without the need for pre-culturing or expansion. Clinical proof-of-principle was established by direct implantation of tumor samples from four patients. Results The resulting ZTX models responded to Erlotinib and Paclitaxel, with similar potency as in mouse-PDX models and the patients themselves, and resistant tumors similarly failed to respond to these drugs in the ZTX system. Drug response was coupled to elevated expression of EGFR, Mdm2, Ptch1 and Tsc1 (Erlotinib), or Nras and Ptch1 (Paclitaxel) and reduced expression of Egfr, Erbb2 and Foxa (Paclitaxel). Importantly, ZTX models retained the invasive phenotypes of the tumors and predicted lymph node involvement of the patients with 91% sensitivity and 62% specificity, which was superior to clinically used tests. The biopsies from all four patient tested implanted successfully, and treatment outcome and dissemination were quantified for all patients in only 3 days. Conclusions We conclude that the ZTX platform provide a fast, accurate, and clinically relevant system for evaluation of treatment outcome and invasion/dissemination of PDX models, providing an attractive platform for combined mouse-zebrafish PDX trials and personalized medicine.
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| 6. |
- Andersson, Mattias K, 1979, et al.
(författare)
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Targeting the Oncogenic Transcriptional Regulator MYB in Adenoid Cystic Carcinoma by Inhibition of IGF1R/AKT Signaling
- 2017
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Ingår i: Jnci-Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 109:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adenoid cystic carcinoma (ACC) is an aggressive cancer with no curative treatment for patients with recurrent/metastatic disease. The MYB-NFIB gene fusion is the main genomic hallmark and a potential therapeutic target. Methods: Oncogenic signaling pathways were studied in cultured cells and/or tumors from 15 ACC patients. Phospho-receptor tyrosine kinase (RTK) arrays were used to study the activity of RTKs. Effects of RTK inhibition on cell proliferation were analyzed with AlamarBlue, sphere assays, and two ACC xenograft models (n = 4-9 mice per group). The molecular effects of MYB-NFIB knockdown and IGF1R inhibition were studied with quantitative polymerase chain reaction, immunoblot, and gene expression microarrays. All statistical tests were two-sided. Results: The MYB-NFIB fusion drives proliferation of ACC cells and is crucial for spherogenesis. Intriguingly, the fusion is regulated through AKT-dependent signaling induced by IGF1R overexpression and is downregulated upon IGF1R-inhibition (% expression of control +/- SD = 27.2 +/- 1.3, P < .001). MYB-NFIB regulates genes involved in cell cycle control, DNA replication/repair, and RNA processing. The transcriptional program induced by MYB-NFIB affects critical oncogenic mediators normally controlled by MYC and is reversed by pharmacological inhibition of IGF1R. Co-activation of epidermal growth factor receptor (EGFR) and MET promoted proliferation of ACC cells, and combined targeting of IGFR1/EGFR/MET induced differentiation and synergistically inhibited the growth of patient-derived xenografted ACCs (ACCX5M1, % growth of control +/- SD = 34.9 +/- 20.3, P = .006; ACCX6, % growth of control +/- SD = 24.1 +/- 17.5, P = .04). Conclusions: MYB-NFIB is an oncogenic driver and a key therapeutic target in ACC that is regulated by AKT-dependent IGF1R signaling. Our studies uncover a new strategy to target an oncogenic transcriptional master regulator and provide new important insights into the biology and treatment of ACC.
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| 7. |
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| 8. |
- Coomans, Marijke B., et al.
(författare)
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Measuring change in health-related quality of life: the impact of different analytical methods on the interpretation of treatment effects in glioma patients
- 2020
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Ingår i: Neuro-Oncology Practice. - : OXFORD UNIV PRESS. - 2054-2577 .- 2054-2585. ; 7:6, s. 668-675
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Tidskriftsartikel (refereegranskat)abstract
- Background. Different analytical methods may lead to different conclusions about the impact of treatment on health-related quality of life (HRQoL). This study aimed to examine 3 different methods to evaluate change in HRQoL and to study whether these methods result in different conclusions. Methods. HRQoL data from 15 randomized clinical trials were combined (CODAGLIO project). Change in HRQoL scores, measured with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and BN20 questionnaires, was analyzed in 3 ways: (1) at the group level, comparing mean changes in scale/item scores between treatment arms, (2) at the patient level per scale/item, calculating the percentage of patients that deteriorated, improved, or remained stable per scale/item, and (3) at the individual patient level, combining all scales/items. Results. Baseline and first follow-up HRQoL data were available for 3727 patients. At the group scale/item level, only the item "hair loss" showed a significant and clinically relevant change (ie, >= 10 points) over time, whereas change scores on the other scales/items were statistically significant only (all P <.001; range in change score, 0.1-6.2). Although a large proportion of patients had stable HRQoL over time (range, 27%-84%) on the patient level per scale/item, many patients deteriorated (range, 6%-43%) or improved (range, 8%-32%) on a specific scale/item. At the individual patient level, the majority of patients (86%) showed both deterioration and improvement, whereas only 1% remained stable on all scales. Conclusions. Different analytical methods of changes in HRQoL result in distinct conclusions of treatment effects, all of which may be relevant for informing clinical decision making.
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| 9. |
- Coomans, Marijke B., et al.
(författare)
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Symptom clusters in newly diagnosed glioma patients: which symptom clusters are independently associated with functioning and global health status?
- 2019
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Ingår i: Neuro-Oncology. - : OXFORD UNIV PRESS INC. - 1522-8517 .- 1523-5866. ; 21:11, s. 1447-1457
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Tidskriftsartikel (refereegranskat)abstract
- Background. Symptom management in glioma patients remains challenging, as patients suffer from various concurrently occurring symptoms. This study aimed to identify symptom clusters and examine the association between these symptom clusters and patients functioning. Methods. Data of the CODAGLIO project was used, including individual patient data from previously published international randomized controlled trials (RCTs) in glioma patients. Symptom prevalence and level of functioning were assessed with European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQ-C30 and QLQ-BN20 self-report questionnaires. Associations between symptoms were examined with Spearman correlation coefficients and partial correlation networks. Hierarchical cluster analyses were performed to identify symptom clusters. Multivariable regression analyses were performed to determine independent associations between the symptom clusters and functioning, adjusted for possible confounders. Results. Included in the analysis were 4307 newly diagnosed glioma patients from 11 RCTs who completed the EORTC questionnaires before randomization. Many patients (44%) suffered from 5-10 symptoms simultaneously. Four symptom clusters were identified: a motor cluster, a fatigue cluster, a pain cluster, and a gastrointestinal/seizures/bladder control cluster. Having symptoms in the motor cluster was associated with decreased (amp;gt;= 10 points difference) physical, role, and social functioning (betas ranged from -11.3 to -15.9, all P amp;lt; 0.001), independent of other factors. Similarly, having symptoms in the fatigue cluster was found to negatively influence role functioning (beta of -12.3, P amp;lt; 0.001), independent of other factors. Conclusions. Two symptom clusters, the fatigue and motor cluster, were frequently affected in glioma patients and were found to independently have a negative association with certain aspects of patients functioning as measured with a self-report questionnaire.
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| 10. |
- Coomans, Marijke, et al.
(författare)
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Factors associated with health-related quality of life (HRQoL) deterioration in glioma patients during the progression-free survival period
- 2022
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 24:12, s. 2159-2169
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Tidskriftsartikel (refereegranskat)abstract
- Background Maintenance of functioning and well-being during the progression-free survival (PFS) period is important for glioma patients. This study aimed to determine whether health-related quality of life (HRQoL) can be maintained during progression-free time, and factors associated with HRQoL deterioration in this period. Methods We included longitudinal HRQoL data from previously published clinical trials in glioma. The percentage of patients with stable HRQoL until progression was determined per scale and at the individual patient level (i.e. considering all scales simultaneously). We assessed time to a clinically relevant deterioration in HRQoL, expressed in deterioration-free survival and time-to-deterioration (the first including progression as an event). We also determined the association between sociodemographic and clinical factors and HRQoL deterioration in the progression-free period. Results Five thousand five hundred and thirty-nine patients with at least baseline HRQoL scores had a median time from randomization to progression of 7.6 months. Between 9-29% of the patients deteriorated before disease progression on the evaluated HRQoL scales. When considering all scales simultaneously, 47% of patients deteriorated on >= 1 scale. Median deterioration-free survival period ranged between 3.8-5.4 months, and median time-to-deterioration between 8.2-11.9 months. For most scales, only poor performance status was independently associated with clinically relevant HRQoL deterioration in the progression-free period. Conclusions HRQoL was maintained in only 53% of patients in their progression-free period, and treatment was not independently associated with this deterioration in HRQoL. Routine monitoring of the patients functioning and well-being during the entire disease course is therefore important, so that interventions can be initiated when problems are signaled.
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