Outcomes of Pelvic Exenteration with en Bloc Partial or Complete Pubic Bone Excision for Locally Advanced Primary or Recurrent Pelvic Cancer.

INTRODUCTION: Neoplasms infiltrating the pubic bone have until recently been considered a contraindication to surgery. Paucity of existing published data in regard to surgical techniques and outcomes exist. OBJECTIVE: This study aims to address outcomes of our recently published technique for en bloc composite pubic bone excision during pelvic exenteration. DESIGN: A prospective database was reviewed to identify patients who underwent a partial or complete pubic bone composite excision over a 12-year period. SETTINGS: This study was conducted at a tertiary level exenteration unit. MAIN OUTCOME MEASURES: Primary outcomes measured were resection margin and survival. Secondary outcomes included patient and operative demographics, type of cancer, extent of pubic bone excision, morbidity, and 30-day mortality. RESULTS: Twenty-nine of over 500 patients undergoing exenterations (mean age, 57.9; 20 males) underwent en bloc complete (11 patients) or partial (18 patients) composite pubic bone excision. Twenty-two patients (76%) underwent resection for recurrent as opposed to advanced primary malignant disease of which rectal adenocarcinoma was the most common followed by squamous-cell carcinoma. The median operating time was 10.5 (range, 6-15) hours, and median blood loss was 2971 (range, 300-8600) mL. Seventeen (59%) patients had a concurrent sacrectomy performed mainly S3 and below. A total cystectomy was performed in 26 patients (90%). Fifteen of 20 male patients (75%) had a perineal urethrectomy. A clear (R0) resection margin was achieved in 22 patients (76%) with a 5-year overall survival of 53% after a median follow-up of 3.2 years (r = 1.4-12.3 years). There was no 30-day mortality. Seventy percent of patients experienced morbidity with a pelvic collection the most common. LIMITATIONS: This study was limited because it was a retrospective review, it occurred at a single site, and it used a small heterogeneous sample. CONCLUSION: Within the realm of evolving exenteration surgery, en bloc composite pubic bone excision offers results comparable to central, lateral, and posterior compartment excisions, and, as such, is a reasonable strategy in the management of neoplasms infiltrating the pubic bone.

Effects of antiplatelet therapy on platelet extracellular vesicle release and procoagulant activity in health and in cardiovascular disease.

Dual antiplatelet therapy with aspirin and clopidogrel is commonly used to prevent recurrent ischemic events in patients with cardiovascular disease. Whilst their effects on platelet reactivity are well documented, it is unclear, however, whether antiplatelet therapy inhibits platelet extracellular vesicle (EV) release. The aim of this study was to investigate the effects of antiplatelet therapy on platelet EV formation and procoagulant activity. Blood samples from 10 healthy controls not receiving antiplatelet therapy were incubated in vitro with aspirin or a P2Y12 inhibitor (MeSAMP). Blood samples from 50 patients receiving long-term dual antiplatelet therapy and undergoing coronary angiography were also studied. Platelet reactivity was assessed by Multiplate™ impedance aggregometry. Platelet EV formation and procoagulant activity of pretreated and untreated blood samples in response to arachidonic acid (AA), adenosine diphosphate (ADP), ADP+PGE1, and thrombin receptor-activating peptide (TRAP) stimulation were assessed by flow cytometry and Procoag-PL assays, respectively. Incubation of normal platelets with aspirin significantly inhibited AA-induced platelet reactivity, EV formation, and procoagulant activity, whilst MeSAMP significantly inhibited platelet reactivity and EV formation in response to AA, ADP, and TRAP, but had minimal effect on procoagulant activity. Most patients receiving dual antiplatelet therapy showed an appropriate reduction in platelet reactivity in response to their treatment; however there was not complete inhibition of increased platelet and EV procoagulant activity in response to ADP, AA, or TRAP. In addition, we could not find any correlation between platelet reactivity and procoagulant activity in patients receiving dual antiplatelet therapy.

Longitudinal changes in hemostatic parameters and reduced pulsatility contribute to non-surgical bleeding in patients with centrifugal continuous-flow left ventricular assist devices.

BACKGROUND: Bleeding and thromboembolic events are identified complications in patients supported with newer centrifugal continuous-flow left ventricular assist devices (cfLVADs). Bleeding events have been associated with acquired von Willebrand syndrome (vWS) in these patients, though longitudinal changes and the effect of pulsatility remain unquantified. We evaluated longitudinal effects of third-generation cfLVADs on hemostatic biomarkers, non-surgical bleeding, and thromboembolic events. We investigated the association between pulsatility (as defined by aortic valve opening) on von Willebrand Factor (VWF) profile and bleeding. METHODS: We prospectively studied 28 patients implanted with the HeartWare (HeartWare International, Framingham, MA) cfLVAD for up to 360 days. We performed bleeding and coagulation assays 8 times from pre-implant to Day 360 (D360) post-implant, including platelet aggregometry, VWF collagen binding activity-to-antigen (CBA/Ag) ratio, thromboelastography, soluble P-selectin, platelet-specific marker soluble glycoprotein VI (sGPVI), and platelet microparticles. Aortic valve opening was assessed by echocardiography at each assessment. Bleeding and thromboembolic events were documented. RESULTS: Bleeding events occurred in 14 patients (50%). Maximal platelet inhibition occurred by D30. VWF profile impairment (VWF CBA/Ag < 0.8) was demonstrated in 89% of patients at D30, with subsequent recovery but further deterioration after D180. Bleeding was associated with elevated pre-implant sGPVI (p = 0.008). Pulsatility was associated with higher VWF CBA/Ag (p = 0.02) and a trend to less bleeding. CONCLUSIONS: Third-generation cfLVADs were associated with longitudinal changes in hemostatic markers, and bleeding was associated with elevated pre-implant plasma sGPVI. Further, pulsatility may contribute to recovery of the VWF profile and potentially lower bleeding risk.