Biorobin

25516640

Recent advances in diagnostic techniques have allowed the diagnosis of gastric cancer (GC) at an early stage. Due to the low incidence of lymph node metastasis and favorable prognosis in early GC, function-preserving surgery which improves postoperative quality of life may be possible. Pylorus-preserving gastrectomy (PPG) is one such function-preserving procedure, which is expected to offer advantages with regards to dumping syndrome, bile reflux gastritis, and the frequency of flatus, although PPG may induce delayed gastric emptying. Proximal gastrectomy (PG) is another function-preserving procedure, which is thought to be advantageous in terms of decreased duodenogastric reflux and good food reservoir function in the remnant stomach, although the incidence of heartburn or gastric fullness associated with this procedure is high. However, these disadvantages may be overcome by the reconstruction method used. The other important problem after PG is remnant GC, which was reported to occur in approximately 5% of patients. Therefore, the reconstruction technique used with PG should facilitate postoperative endoscopic examinations for early detection and treatment of remnant gastric carcinoma. Oncologic safety seems to be assured in both procedures, if the preoperative diagnosis is accurate. Patient selection should be carefully considered. Although many retrospective studies have demonstrated the utility of function-preserving surgery, no consensus on whether to adopt function-preserving surgery as the standard of care has been reached. Further prospective randomized controlled trials are necessary to evaluate survival and postoperative quality of life associated with function-preserving surgery.

Gastric cancer, Function preserving surgery, Quality of life, Pylorus preserving surgery, Proximal gastrectomy

Current status of function-preserving surgery for gastric cancer

akuro Saito, Yukinori Kurokawa, Shuji Takiguchi, Masaki Mori, and Yuichiro Doki

2014 Dec 14;

23197721

γ-Secretase inhibition represents a major therapeutic strategy for lowering amyloid β (Aβ) peptide production in Alzheimer’s disease (AD). Progress toward clinical use of γ-secretase inhibitors has, however, been hampered due to mechanism-based adverse events, primarily related to impairment of Notch signaling. The γ-secretase inhibitor MRK-560 represents an exception as it is largely tolerable in vivo despite displaying only a small selectivity between Aβ production and Notch signaling in vitro. In exploring the molecular basis for the observed tolerability, we show that MRK-560 displays a strong preference for the presenilin 1 (PS1) over PS2 subclass of γ-secretases and is tolerable in wild-type mice but causes dose-dependent Notch-related side effect in PS2-deficient mice at drug exposure levels resulting in a substantial decrease in brain Aβ levels. This demonstrates that PS2 plays an important role in mediating essential Notch signaling in several peripheral organs during pharmacological inhibition of PS1 and provide preclinical in vivo proof of concept for PS2-sparing inhibition as a novel, tolerable and efficacious γ-secretase targeting strategy for AD

Alzheimer's Disease: Presenilin 2-Sparing γ-Secretase Inhibition Is a Tolerable Aβ Peptide-Lowering Strategy

Tomas Borgegard,1,* Susanne Gustavsson,1,* Charlotte Nilsson,1,* Santiago Parpal,1,* Rebecka Klintenberg,1,* Anna-Lena Berg,1,* Susanne Rosqvist,1 Lutgarde Serneels,2,3 Samuel Svensson,1,8,9 Fredrik Olsson,1 Shaobo Jin,4 Hongmei Yan,1 Johanna Wanngren,5 Anders Jureus,1 Anna Ridderstad-Wollberg,1 Patrik Wollberg,1 Kenneth Stockling,1 Helena Karlstrom,5 asa Malmberg,1 Johan Lund,1 Per I. Arvidsson,1,6,7 Bart De Strooper,2,3 Urban Lendahl,corresponding author4 and Johan Lundkvistcorresponding author1,5,9

2012 Nov 28;