A possible association between aprotinin and improved survival after radical surgery for mesothelioma

Abstract

Background Aprotinin has been used to decrease blood loss with complicated cardiac surgery but has not been investigated in extrapleural pneumonectomy, an operation that does not use cardiopulmonary bypass. In this prospective, randomized, placebo-controlled, double-blind trial, the authors investigated whether aprotinin decreased blood loss in patients who underwent this operation. Methods After appropriate statistical design and institutional review board approval, eligible patients who were scheduled for extrapleural pneumonectomy were randomized to receive either aprotinin or placebo during the operation. Blood loss and survival data were obtained from electronic medical records and surgical databases. Results Of 20 patients who were enrolled, 16 patients met criteria for blood loss analysis. Four patients were excluded from the blood loss analysis: Three patients were inoperable because of tumor spread and underwent limited surgery, and 1 patient died intraoperatively because of acute, massive hemorrhage. The mean blood loss was 769 mL with aprotinin versus 1832 mL with placebo (P = .05; Wilcoxon test). All 20 patients were included in survival analyses. All 9 patients who received placebo died. In contrast, 7 of 11 patients who received aprotinin remained alive at the time of the current report. Kaplan-Meier survival curves differed significantly between the 2 groups (P = .0004). A Bayesian multivariate survival analysis of 18 patients who had complete data available on 8 prognostic variables indicated a posterior probability of .99 that aprotinin was beneficial. Conclusions Aprotinin decreased blood loss. After accounting for covariate effects, there was a significant comparative benefit with aprotinin in postoperative survival. This finding was unexpected and could not be considered conclusive because of the small size of the current study. A confirmatory study may be warranted.

Prognostic value of plasma d-dimer levels in patients with glioblastoma multiforme – Results from a pilot study

“…Th e activity of the uPA/uPAR system may thus drive both tumor progression and d-dimer levels. If so, this might be a direct target to a novel and potentially highly eff ective and non-toxic form of treatment for GBM [22].…”

“…Focusing on molecular markers, only the methylation status of the O 6 -methylguanine methyltransferase (MGMT) gene has shown a signifi cant association with survival in patients with GBM [4,22]. In patients with colorectal cancer, elevated d-dimer levels were signifi cantly associated with survival [14,15].…”

Does regional anaesthesia and analgesia or opioid analgesia influence recurrence after primary cancer surgery? An update of available evidence

“…There is some evidence that aprotinin, a serine protease inhibitor with UPA-inhibitory effects, may improve cancer survival if used in the perioperative setting. [133] Moreover, the activation of specific genes ("genetic switching") during the perioperative period is theorised to contribute to cancer recurrence. Breast cancer cells, which express MOR, demonstrated a morphine-induced increase in cell migration, possibly mediated by the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 Moreover, the NO pathway is associated with morphine"s induction of apoptosis in human endothelial cells, with activation of nuclear factor (NF)-κB.…”

Blood Loss and Massive Transfusion in Patients Undergoing Major Oncological Surgery: What Do We Know?

“…Reported estimated blood loss [38][39][40][41][42][43] 400-12,100 2-10 Sacral tumors [44][45][46] 3,000-37,000 0-43 Hemipelvectomy [47][48][49][50] 400-12,100 0-134 Total pelvic exenterations [47][48][49][50] 900-9,500 0-18 Nephrectomy with IVC embolectomy [37,[51][52][53][54][55] 200−16,000 0−91 Liver and multivisceral resection [12,[56][57][58][59][60][61][62] 200->5,000 0-44 Extrapleural pneumonectomies [63][64][65] 900-65,00 0-18 Table 1 illustrates ranges of blood losses and PRBCs of transfused units reported in the literature.…”

“…Investigators from our institution studied the role of aprotinin in intraoperative blood loss in patients with mesothelioma undergoing extrapleural pneumonectomy. Despite the trial being interrupted due to withdrawal of aprotinin from the market by the manufacturer, the authors reported that aprotinin decreased blood loss compared to placebo [64] (Table 2).…”