Transfusion of salvaged red blood cells during pancreatic ductal adenocarcinoma operations.
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ABSTRACT:
SUBMITTER: Goel N
PROVIDER: S-EPMC10361671 | biostudies-literature | 2023 Jul
REPOSITORIES: biostudies-literature
Publications
Transfusion of salvaged red blood cells during pancreatic ductal adenocarcinoma operations.
Goel Neha N Rhim Andrew D AD Xi Huaqing H Olive Kenneth P KP Thomas Alexander S AS Kwon Wooil W Schwartz Joseph J Sugahara Kazuki N KN Schrope Beth A BA Chabot John A JA Kluger Michael D MD
The British journal of surgery 20230701 8
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Project description:Both cardiopulmonary bypass (CPB) and red blood cell (RBC) storage are associated with detrimental changes in RBC structure and function that may adversely affect tissue oxygen delivery. We tested the hypothesis that in cardiac surgery patients, RBC deformability and aggregation are minimally affected by CPB with autologous salvaged blood alone but are negatively affected by the addition of stored allogeneic blood.In this prospective cohort study, 32 patients undergoing cardiac surgery with CPB were divided into 3 groups by transfusion status: autologous salvaged RBCs alone (Auto; n = 12), autologous salvaged RBCs + minimal (<5 units) stored allogeneic RBCs (Auto+Allo min; n = 10), and autologous salvaged RBCs + moderate (?5 units) stored allogeneic RBCs (Auto+Allo mod; n = 10). Ektacytometry was used to measure RBC elongation index (deformability) and critical shear stress (aggregation) before, during, and for 3 days after surgery.In the Auto group, RBC elongation index did not change significantly from the preoperative baseline. In the Auto+Allo min group, mean elongation index decreased from 32.31 ± 0.02 (baseline) to 30.47 ± 0.02 (nadir on postoperative day 1) (P = 0.003, representing a 6% change). In the Auto+Allo mod group, mean elongation index decreased from 32.7 ± 0.02 (baseline) to 28.14 ± 0.01 (nadir on postoperative day 1) (P = 0.0001, representing a 14% change). Deformability then dose-dependently recovered toward baseline over the first 3 postoperative days. Changes in aggregation were unrelated to transfusion (no difference among groups). For the 3 groups combined, mean critical shear stress decreased from 359 ± 174 mPa to 170 ± 141 mPa (P = 0.01, representing a 54% change), with the nadir at the end of surgery and returned to baseline by postoperative day 1.In cardiac surgery patients, transfusion with stored allogeneic RBCs, but not autologous salvaged RBCs, is associated with a decrease in RBC cell membrane deformability that is dose-dependent and may persist beyond 3 postoperative days. These findings suggest that autologous salvaged RBCs may be of higher quality than stored RBCs, since the latter are subject to the so-called storage lesions.
| S-EPMC4041165 | biostudies-other
Project description:Background/objectivesThe vascular heterogeneity of pancreatic ductal adenocarcinoma (PDAC) has never been characterised. We analysed the heterogeneous vascular density of human PDAC along with its prognostic correlation.MethodsTissue Microarrays of 87 patients with different pancreatico-biliary pathologies were analysed in an automated manner (Ariol™) after CD31 staining to assess vascular density in juxta-tumoral and panstromal compartments. In vitro and ex vivo assays were carried out to assess the role of PSC.ResultsPDAC has a distinct vascular density and distribution of vessels compared to cholangiocarcinoma. The PDAC juxta-tumoral stroma was hypovascular and the normal adjacent rim was hypervascular compared to the panstromal compartment. These features adversely affected patient prognosis, suggesting a model for spatio-temporal PDAC evolution. Mice aortic rings and 3D organotypic cultures demonstrated pro- and anti-angiogenic signalling from activated PSC and cancer cells respectively. ATRA-induced quiescence suppressed the pro-angiogenic activity of PSC.ConclusionHuman PDAC has variable vascularity at microscopic level suggesting that novel stromal directed therapies would need to be determined by pathological characteristics.
| S-EPMC5123629 | biostudies-literature
Project description:ObjectiveTo evaluate survival outcomes associated with perioperative allogeneic red blood cell transfusion (RBCT) in patients with pancreatic ductal adenocarcinoma undergoing surgery.MethodsPubMed, Embase, Cochrane, and Web of Science Core Collection were queried for English-language articles until May 28, 2020. Studies evaluating long-term outcomes of RBCT compared with no transfusion in adults with pancreatic ductal adenocarcinoma undergoing pancreatectomy were included. E-value sensitivity analysis assessed the potential for unmeasured confounders to overcome these findings.ResultsOf 4379 citations, 5 retrospective cohort studies were included. Three studies reported shorter recurrence-free survival by 1 to 5 months with RBCT. Two studies found shorter disease-specific survival by 5 to 13 months with RBCT. Overall survival was reduced by 5 to 7 months with RBCT in 3 studies. All multivariable findings associated with RBCT could be readily overcome unmeasured confounding on sensitivity analysis. Confounding in baseline characteristics resulted in high risk of bias.ConclusionsImprecision, unmeasured confounding, small effect sizes, and overall low quality of the available literature result in uncertainty regarding the effect of transfusion on recurrence-free survival, disease-specific survival, and overall survival in patients undergoing surgery for pancreatic cancer. Randomized trials are needed to determine if there is a causal relationship between transfusion and survival after pancreatic resection.
| S-EPMC8375579 | biostudies-literature
Project description:BACKGROUND AND AIMS: Pancreaticoduodenectomy (PD) is a major operative intervention performed most commonly for malignancy in the head of pancreas. The aim of this study was to evaluate the utilization of blood transfusion for PD and to determine whether this had prognostic significance in a subset of patients with pancreatic ductal adenocarcinoma (PDAC). MATERIAL AND METHODS: Data on blood transfusion requirement were retrospectively collected for patients undergoing PD from 1998 to 2005. Standard prognostic factors and survival data were also collected in patients with PDAC. RESULTS: One-hundred-and-seventy patients underwent PD. Seventy-six patients (45%) received transfusion. The median (interquartile range) number of units of red cell concentrate (RCC) transfused perioperatively (intraoperatively and within 24 h of surgery) was 1.5 (0.5-2.5). The median preoperative haemoglobin (Hb) was 126 g/dl. The median number of units of RCC transfused perioperatively in patients with Hb <126 g/dl was 2 (1-3); for those with Hb > or = 126 g/dl the median was 0 (0-1); p=0.003. Forty-nine patients who were resected for PDAC were subjected to survival analysis. Univariate and multivariate analyses showed that only posterior resection margin invasion was associated with an adverse outcome (margin positive 198 [143-470] days vs margin negative 398 [303-859] days; p=0.02). Perioperative RCC transfusion requirement was not a significant predictor of survival (transfusion 408 [214-769] days vs no transfusion 331 [217-391] days; p=0.18). Furthermore, RCC transfusion within 30 days of operation was not a significant predictor of poor survival (transfusion 331 [201-459] days vs no transfusion 317 [196-769] days; p=0.43). CONCLUSIONS: PD can be performed with a moderately low requirement for RCC transfusion; however, low preoperative haemoglobin is a predictor for the requirement of RCC transfusion. Administration of RCC transfusion does not appear to be a significant adverse prognostic factor in patients with resected PDAC.
| S-EPMC2215364 | biostudies-other
Project description:BackgroundThis study aims to test associations between perioperative blood transfusion and postoperative morbidity and mortality after major abdominal operations.MethodsThe 2014 ACS NSQIP dataset was queried for all patients who underwent one of the ten major abdominal operations. Separate multivariable regression models, were developed to evaluate the independent effects of perioperative blood transfusion on morbidity and mortality.ResultsOf 48,854 patients in the study cohort, 4887 (10%) received a blood transfusion. Rates of transfusion ranged from 4% for laparoscopic gastrointestinal resection to 58% for open AAA. After adjusting for significant effects of NSQIP-estimated probabilities, transfusion was independently associated with morbidity and mortality after open AAA repair (OR = 1.99/14.4 respectively, p ≤ 0.010), esophagectomy (OR = 2.80/3.0, p < 0.001), pancreatectomy (OR = 1.88/3.01, p < 0.001), hepatectomy (OR = 2.82/5.78, p < 0.001), colectomy (OR = 2.15/3.17, p < 0.001), small bowel resection (OR = 2.81/3.83, p ≤ 0.004), and laparoscopic gastrointestinal operations (OR = 2.73/4.05, p < 0.001).ConclusionsPerioperative blood transfusion is independently associated with an increased risk of morbidity and mortality after most major abdominal operations.
| S-EPMC6097952 | biostudies-literature
Project description:Although a subset of recent studies have suggested that red blood cell (RBC) storage length is associated with adverse patient outcomes, others have shown no such relationship. Adults may be transfused with RBC units of different storage lengths, and existing studies do not take into consideration that fresh RBCs may alter responses to concurrently transfused stored RBCs. To test this possibility, we utilized a murine model and investigated transfusion outcomes of fresh, stored, or fresh-plus-stored RBCs.Fresh, 14-day-stored or fresh plus 14-day-stored leukoreduced RBCs from HOD-transgenic donors (with RBC-specific expression of hen egg lysozyme, ovalbumin, and human Duffy(b)) were transfused into naïve C57BL/6 recipients. Serum cytokines and anti-HOD alloimmunization were evaluated after transfusion.In six of six experiments (n = 90 mice total), a proinflammatory serum cytokine storm of interleukin-6, keratinocyte-derived chemokine/CXCL1, and monocyte chemoattractant protein-1 was observed in transfusion recipients of stored but not fresh RBCs, along with high degrees of anti-HOD alloimmunization. However, concurrent transfusion of fresh HOD RBCs along with stored HOD RBCs significantly decreased these adverse outcomes (p < 0.05).These results are consistent with fresh murine HOD RBCs losing protective properties during storage, and introduce a previously unrecognized variable in RBC storage studies. If translatable to humans, uniform "old blood" groups may be needed in future clinical studies to more accurately investigate the biologic effects of older RBC units.
| S-EPMC3175330 | biostudies-other
Project description: Not available
| S-EPMC8691808 | biostudies-literature
Project description:IntroductionFocal adhesion kinase (FAK) is a nonreceptor tyrosine kinase protein frequently overexpressed in cancer and has been linked to an increase in the stem cell population of tumors, resistance to therapy, and metastatic spread. Pharmacological FAK inhibition in pancreatic cancer has received increased attention over the last few years, either alone or in combination with other therapeutics including chemotherapy and immunotherapy. However, its prognostic value and its role in radioresistance of pancreatic ducal adenocarcinoma (PDAC) is unknown.Methods and materialsUsing the TCGA and GTEx databases, we investigated the genetic alterations and mRNA expression levels of PTK2 (the encoding-gene for FAK) in normal pancreatic tissue and pancreatic cancer and its impact on patient survival. Furthermore, we evaluated the expression of FAK and its tyrosine domain Ty-397 in three pancreatic cancer cell lines. We went further and evaluated the role of a commercial FAK tyrosine kinase inhibitor VS-4718 on the viability and radiosensitization of the pancreatic cell lines as well as its effect on the extracellular matrix (ECM) production from the pancreatic stellate cells. Furthermore, we tested the effect of combining radiation with VS-4718 in a three-dimensional (3D) multicellular pancreatic tumor spheroid model.ResultsA database analysis revealed a relevant increase in genetic alterations and mRNA expression of the PTK2 in PDAC, which were associated with lower progression-free survival. In vitro, there was only variation in the basal phosphorylation level of FAK in cell lines. VS-4718 radiosensitized pancreatic cell lines only in the presence of ECM-producing pancreatic stellate cells and markedly reduced the ECM production in the stromal cells. Finally, using a 3D multicellular tumor model, the combination of VS-4718 and radiotherapy significantly reduced the growth of tumor aggregates.ConclusionPharmacological inhibition of FAK in pancreatic cancer could be a novel therapeutic strategy as our results show a radiosensitization effect of VS-4718 in vitro in a multicellular 2D- and in a 3D-model of pancreatic cancer.
| S-EPMC7801360 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive type of pancreatic cancer (PCa) with a low survival rate. microRNAs (miRs) are endogenous, non-coding RNAs that moderate numerous biological processes. miRs have been associated with the chemoresistance and metastasis of PDAC and the presence of a subpopulation of highly plastic "stem"-like cells within the tumor, known as cancer stem cells (CSCs). In this study, we investigated the role of miR-21, which is highly expressed in Panc-1 and MiaPaCa-2 PDAC cells in association with CSCs. Following miR-21 knockouts (KO) from both MiaPaCa-2 and Panc-1 cell lines, reversed expressions of epithelial-mesenchymal transition (EMT) and CSCs markers were observed. The expression patterns of key CSC markers, including CD44, CD133, CX-C chemokine receptor type 4 (CXCR4), and aldehyde dehydrogenase-1 (ALDH1), were changed depending on miR-21 status. miR-21 (KO) suppressed cellular invasion of Panc-1 and MiaPaCa-2 cells, as well as the cellular proliferation of MiaPaCa-2 cells. Our data suggest that miR-21 is involved in the stemness of PDAC cells, may play roles in mesenchymal transition, and that miR-21 poses as a novel, functional biomarker for PDAC aggressiveness.
| S-EPMC8835847 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma
| PRJNA432344 | ENA