| 1. |
- Adam, René, et al.
(författare)
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Managing synchronous liver metastases from colorectal cancer : A multidisciplinary international consensus
- 2015
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Ingår i: Cancer Treatment Reviews. - : Elsevier BV. - 0305-7372 .- 1532-1967. ; 41:9, s. 729-741
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Tidskriftsartikel (refereegranskat)abstract
- An international panel of multidisciplinary experts convened to develop recommendations for managing patients with colorectal cancer (CRC) and synchronous liver metastases (CRCLM). A modified Delphi method was used. CRCLM is defined as liver metastases detected at or before diagnosis of the primary CRC. Early and late metachronous metastases are defined as those detected ⩽12months and >12months after surgery, respectively. To provide information on potential curability, use of high-quality contrast-enhanced computed tomography (CT) before chemotherapy is recommended. Magnetic resonance imaging is increasingly being used preoperatively to aid detection of subcentimetric metastases, and alongside CT in difficult situations. To evaluate operability, radiology should provide information on: nodule size and number, segmental localization and relationship with major vessels, response after neoadjuvant chemotherapy, non-tumoral liver condition and anticipated remnant liver volume. Pathological evaluation should assess response to preoperative chemotherapy for both the primary tumour and metastases, and provide information on the tumour, margin size and micrometastases. Although the treatment strategy depends on the clinical scenario, the consensus was for chemotherapy before surgery in most cases. When the primary CRC is asymptomatic, liver surgery may be performed first (reverse approach). When CRCLM are unresectable, the goal of preoperative chemotherapy is to downsize tumours to allow resection. Hepatic resection should not be denied to patients with stable disease after optimal chemotherapy, provided an adequate liver remnant with inflow and outflow preservation remains. All patients with synchronous CRCLM should be evaluated by a hepatobiliary multidisciplinary team.
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| 2. |
- Aguilar, Helena, et al.
(författare)
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VAV3 mediates resistance to breast cancer endocrine therapy
- 2014
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Ingår i: Breast Cancer Research. - : BioMed Central. - 1465-5411 .- 1465-542X. ; 16:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor alpha (ERalpha) are among the most effective systemic treatments for ERalpha-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through mechanisms that involve ERalpha transcriptional regulatory plasticity. Here, we identify VAV3 as a critical component in this process.METHODS: A cell-based chemical compound screen was carried out to identify therapeutic strategies against resistance to endocrine therapy. Binding to ERalpha was evaluated by molecular docking analyses, an agonist fluoligand assay, and short-hairpin (sh) RNA-mediated protein depletion. Microarray analyses were performed to identify altered gene expression. Western blot of signaling and proliferation markers and shRNA-mediated protein depletion in viability and clonogenic assays were performed to delineate the role of VAV3. Genetic variation in VAV3 was assessed for association with the response to tamoxifen. Immunohistochemical analyses of VAV3 were carried out to determine the association with therapy response and different tumor markers. An analysis of gene expression association with drug sensitivity was carried out to identify a potential therapeutic approach based on differential VAV3 expression.RESULTS: The compound YC-1 was found to comparatively reduce the viability of cell models of acquired resistance. This effect was probably not due to activation of its canonical target (soluble guanylyl cyclase) but instead a result of binding to ERalpha. VAV3 was selectively reduced upon exposure to YC-1 or ERalpha depletion and, accordingly, VAV3 depletion comparatively reduced the viability of cell models of acquired resistance. In the clinical scenario, germline variation in VAV3 was associated with response to tamoxifen in Japanese breast cancer patients (rs10494071 combined P value = 8.4 x 10-4). The allele association combined with gene expression analyses indicated that low VAV3 expression predicts better clinical outcome. Conversely, high nuclear VAV3 expression in tumor cells was associated with poorer endocrine therapy response. Based on VAV3 expression levels and the response to erlotinib in cancer cell lines, targeting EGFR signaling may be a promising therapeutic strategy.CONCLUSIONS: This study proposes VAV3 as a biomarker and rationale signaling target to prevent and/or overcome resistance to endocrine therapy in breast cancer.
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| 3. |
- Borras, Josep M, et al.
(författare)
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Innovation, value and reimbursement in radiation and complex surgical oncology: Time to rethink.
- 2022
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Ingår i: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. - : Elsevier BV. - 1532-2157. ; 48:5, s. 967-977
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Forskningsöversikt (refereegranskat)abstract
- Complex surgery and radiotherapy are the central pillars of loco-regional oncology treatment. This paper describes the reimbursement schemes used in radiation and complex surgical oncology, reports on literature and policy reviews.A systematic review of the literature of the reimbursement models has been carried out separately for radiotherapy and complex cancer surgery based on PRISMA guidelines. Using searches of PubMed and grey literature, we identified articles from scientific journals and reports published since 2000 on provider payment or reimbursement systems currently used in radiation oncology and complex cancer surgery, also including policy models.Most European health systems reimburse radiotherapy using a budget-based, fee-for-service or fraction-based system; while few reimburse services according to an episode-based model. Also, the reimbursement models for cancer surgery are mostly restricted to differences embedded in the DRG system and adjustments applied to the fees, based on the complexity of each surgical procedure. There is an enormous variability in reimbursement across countries, resulting in different incentives and different amounts paid for the same therapeutic strategy.A reimbursement policy, based on the episode of care as the basic payment unit, is advocated for. Innovation should be tackled in a two-tier approach: one defining the common criteria for reimbursement of proven evidence-based interventions; another for financing emerging innovation with uncertain definitive value. Relevant clinical and economic data, also collected real-life, should support reimbursement systems that mirror the actual cost of evidence-based practice.
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| 4. |
- Martin, David, et al.
(författare)
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Defining Major Surgery: A Delphi Consensus Among European Surgical Association (ESA) Members
- 2020
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 44:7, s. 2211-2219
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Tidskriftsartikel (refereegranskat)abstract
- © 2020, Société Internationale de Chirurgie. Background: Major surgery is a term frequently used but poorly defined. The aim of the present study was to reach a consensus in the definition of major surgery within a panel of expert surgeons from the European Surgical Association (ESA). Methods: A 3-round Delphi process was performed. All ESA members were invited to participate in the expert panel. In round 1, experts were inquired by open- and closed-ended questions on potential criteria to define major surgery. Results were analyzed and presented back anonymously to the panel within next rounds. Closed-ended questions in round 2 and 3 were either binary or statements to be rated on a Likert scale ranging from 1 (strong disagreement) to 5 (strong agreement). Participants were sent 3 reminders at 2-week intervals for each round. 70% of agreement was considered to indicate consensus. Results: Out of 305 ESA members, 67 (22%) answered all the 3 rounds. Significant comorbidities were the only preoperative factor retained to define major surgery (78%). Vascular clampage or organ ischemia (92%), high intraoperative blood loss (90%), high noradrenalin requirements (77%), long operative time (73%) and perioperative blood transfusion (70%) were procedure-related factors that reached consensus. Regarding postoperative factors, systemic inflammatory response (76%) and the need for intensive or intermediate care (88%) reached consensus. Consequences of major surgery were high morbidity (>30% overall) and mortality (>2%). Conclusion: ESA experts defined major surgery according to extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcomes.
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