Akimasa Nishimura

Plasma Exchange-based Plasma Recycling Dialysis System as an Artificial Liver Support

Abstract:  We developed a plasma recycling dialysis (PRD) system based on plasma exchange (PE). In this system, rapid reduction of toxic substances and restitution of deficient essential substances are performed by PE and subsequent blood purification is performed by dialysis between separated plasma recycled over a purification device and the patients blood across the membrane of a plasma separator. To demonstrate the safety and efficacy of this system, we used a pig model of fulminant hepatic failure (FHF) and anion exchange resin, activated charcoal and hemodialysis for the purification device. FHF was induced by intraportal administration of α‐amanitine (0.1 mg/kg) and lipopolysaccharides (1 µg/kg) in pigs. Three groups of animals were studied: group 1, diseased controls (N = 4); group 2, PE group (N = 4), 16 h after drug infusion the pigs underwent PE of approximately 1.2 L for 2 h; and group 3, PE + PRD group (N = 4), the pigs underwent PE followed by PRD for 6 h. The hemodynamic status of all animals was stable during the procedure. In group 3, the values of ammonia, total bile acid and total bilirubin continuously decreased and were significantly lower than those of the animals in group 2 24 h after the induction of FHF. The Fischer ratio was significantly higher than in group 2 after 24 h. Group 3 pigs maintained a higher level of consciousness and survived longer than group 2 pigs. Safety of this PE‐based PRD system was demonstrated and the removal of toxic substances was significant. This study confirmed the clinical utility of this system as an artificial liver support.

PO76 THERAPEUTIC STRATEGY FOR RECURRENT HER2-POSITIVE BREAST CANCER PATIENTS

disease course can be controlled by endocrine agents in relation to the overall palliative survival time. Methods: From a non-selected cohort of women who were treated at the University Women’s Hospital Basel for newly diagnosed BC in a 20year period (1990-2009), we analyzed 205 consecutive patients who had or developed distant metastatic HR-positive disease over a 15-year period (1997-2011). In order to give a quantitative description of the overall duration of ET in relation to palliative survival time, we evaluated the “cumulative time of palliative endocrine therapy” (CTPET). When patients received several lines of ET, the duration of each line was added to the CTPET. In a further step, we calculated the ratio between CTPET and metastatic disease survival time (MDS). This ratio describes the percentage of the patient’s survival time after diagnosis of metastatic disease during which endocrine therapy had been administered as the only systemic therapy. The CTPET/MDS ratio was only analyzed in patients who had a survival time of at least nine months (n=145, 87.9%). Results: 165 patients (80.5%) received ET as a part of palliative care. The median number of therapy lines was two (range: 1-7). The median duration was 18 months (range 0.5-133 months). The median metastatic disease survival (MDS) was 34 months (range: 1-137 months). The median CTPET/MDS ratio was 70.6 (range 2.1-100). Patients who were therapy-naive had a higher ratio (p=0.002) than those who were not. Discussion: ET is widely applied in palliative cases of HR-positive BC. Only in approximately 20% of cases was this option not carried out. In particular, patients who were ET-naive responded well to palliative ET. If metastatic BC could be stabilized in such a way that the palliative situation could be viewed as a chronic disease process, then effective ET formed an important cornerstone in their management; in general, the longer disease progression was suppressed by ET, the longer the MDS. With this study, we introduced the CTPET/MDS ratio into the literature. In our opinion, this is a promising quantitative measure of how long the metastatic disease course can be controlled by agents which offer, compared to chemotherapy, many advantages (safety, efficacy, convenience, favorable side-effect profile). After excluding those patients with rapidly progressive courses, our data showed that the disease was controlled and stabilized for about 70% of the entire palliative course with ET alone.