The prognosis of incurable cachectic cancer patients on home parenteral nutrition: A multi-centre observational study with prospective follow-up of 414 patients

Background: The role of home parenteral nutrition (HPN) in incurable cachectic cancer patients unable to eat is extremely controversial. The aim of this study is to analyse which factors can influence the outcome. Patients and methods: We studied prospectively 414 incurable cachectic (sub)obstructed cancer patients receiving HPN and analysed the association between patient or clinical characteristics and surviving status. Results: Median weight loss, versus pre-disease and last 6-month period, was 24% and 16%, respectively. Median body mass index was 19.5, median KPS was 60, median life expectancy was 3 months. Mean/median survival was 4.7/3.0 months; 50.0% and 22.9% of patients survived 3 and 6 months, respectively. At the multivariable analysis, the variables significantly associated with 3- and 6-month survival were Glasgow Prognostic Score (GPS) and KPS, and GPS, KPS and tumour spread, respectively. By the aggregation of the significant variables, it was possible to dissect several classes of patients with different survival probabilities. Conclusions: The outcome of cachectic incurable cancer patients on HPN is not homogeneous. It is possible to identify groups of patients with a ≥6-month survival (possibly longer than that allowed in starvation). The indications for HPN can be modulated on these clinical/biochemical indices. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Polymeric photosensitizer-embedded self-expanding metal stent for repeatable endoscopic photodynamic therapy of cholangiocarcinoma

Photodynamic therapy (PDT) is a new therapeutic approach for the palliative treatment of malignant bile duct obstruction. In this study, we designed photosensitizer-embedded self-expanding nonvascular metal stent (PDT-stent) which allows repeatable photodynamic treatment of cholangiocarcinoma without systemic injection of photosensitizer. Polymeric photosensitizer (pullulan acetate-conjugated pheophorbide A; PPA) was incorporated in self-expanding nonvascular metal stent. Residence of PPA in the stent was estimated in buffer solution and subcutaneous implantation on mouse. Photodynamic activity of PDT-stent was evaluated through laserexposure on stent-layered tumor cell lines, HCT-116 tumor-xenograft mouse models and endoscopic intervention of PDT-stent on bile duct of mini pigs. Photo-fluorescence imaging of the PDT-stent demonstrated homogeneous embedding of polymeric Pheo-A (PPA) on stent membrane. PDT-stent sustained its photodynamic activities at least for 2 month. And which implies repeatable endoscopic PDT is possible after stent emplacement. The PDT-stent after light exposure successfully generated cytotoxic singlet oxygen in the surrounding tissues, inducing apoptotic degradation of tumor cells and regression of xenograft tumors on mouse models. Endoscopic biliary in-stent photodynamic treatments on minipigs also suggested the potential efficacy of PDT-stent on cholangiocarcinoma. In vivo and in vitro studies revealed our PDT-stent, allows repeatable endoscopic biliary PDT, has the potential for the combination therapy (stent plus PDT) of cholangiocarcinoma. © 2014 Elsevier Ltd.

SLAT regulates Th1 and Th2 inflammatory responses by controlling Ca2+/NFAT signaling

SWAP-70-like adapter of T cells (SLAT) is a novel guanine nucleotide exchange factor for Rho GTPases that is upregulated in Th2 cells, but whose physiological function is unclear. We show that SLAT-/- mice displayed a developmental defect at one of the earliest stages of thymocyte differentiation, the double-negative 1 (DN1) stage, leading to decreased peripheral T cell numbers. SLAT-/- peripheral CD4+ T cells demonstrated impaired TCR/CD28-induced proliferation and IL-2 production, which was rescued by the addition of exogenous IL-2. Importantly, SLAT-/- mice were grossly impaired in their ability to mount not only Th2, but also Th1-mediated lung inflammatory responses, as evidenced by reduced airway neutrophilia and eosinophilia, respectively. Levels of Th1 and Th2 cytokine in the lungs were also markedly reduced, paralleling the reduction in pulmonary inflammation. This defect in mounting Th1/Th2 responses, which was also evident in vitro, was traced to a severe reduction in Ca2+ mobilization from ER stores, which consequently led to defective TCR/CD28-induced translocation of nuclear factor of activated T cells 1/2 (NFATc1/2). Thus, SLAT is required for thymic DN1 cell expansion, T cell activation, and Th1 and Th2 inflammatory responses.