Patient-reported outcomes in palliative gastrointestinal stenting: a Norwegian multicenter study

Background The clinical effect of stent treatment has been evaluated by mainly physicians; only a limited number of prospective studies have used patient-reported outcomes for this purpose. The aim of this work was to study the clinical effect of self-expanding metal stents in treatment of malignant gastrointestinal obstructions, as evaluated by patient-reported outcomes, and compare the rating of the treatment effect by patients and physicians. Methods Between November 2006 and April 2008, 273 patients treated with SEMS for malignant GI and biliary obstructions were recruited from nine Norwegian hospitals. Patients and physicians assessed symptoms independently at the time of treatment and after 2 weeks using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire supplemented with specific questions related to obstruction. Results A total of 162 patients (99 males; median age = 72 years) completed both assessments and were included in the study. A significant improvement in the mean global health score was observed after 2 weeks (from 9 to 18 on a 0–100 scale, P\0.03) for all stent locations. Both patients and physicians reported a significant reduction in all obstruction-related symptoms ([20 on the 0–100 scale, P\0.006) after SEMS treatment. The physicians reported a larger mean improvement in symptoms than did the patients, mainly because they reported more severe symptoms before treatment. Conclusion SEMS treatment is effective in relieving symptoms of malignant GI and biliary obstruction, as reported by patients and physicians. The physicians, however, reported a larger reduction in obstructive symptoms than did the patients. A prospective assessment of patientreported outcomes is important in evaluating SEMS treatment

Quality of life in patients with achalasia: Associations with Eckardt score and objective treatment outcomes after peroral endoscopic myotomy

Background and study aims Knowledge on self-reported quality of life (QoL) in achalasia and QoL improvements after peroral endoscopic myotomy (POEM) is limited. Furthermore, the clinical role of QoL in achalasia follow-up has not been evaluated. The present study aimed to examine QoL in achalasia patients before and after POEM and assess associations between QoL, Eckardt score (ES) and objective results. Patients and methods This was a single-center prospective study of treatment-naïve achalasia patients with 12-month follow-up after POEM including manometry, upper endoscopy, 24-hour pH registration, and timed barium esophagogram. QoL data were registered using European Organisation for Research and Treatment of Cancer core questionnaire (QLQ-C30) and esophageal module (QLQ-OES18). Comparison with a reference population was performed to assess impact of achalasia on QoL and effect of therapy. Mixed models for repeated measures were applied. Results Fifty patients (26 females) with a median age of 47 years (18–76) were included. Before treatment, all QoL domains were significantly impaired compared with an age- and gender-adjusted reference population (P < 0.05). No significant QoL-differences were found after POEM, except for fatigue and nausea/vomiting. Clinically relevant QoL improvement was observed in ≥ 50 % of the patients in all QoL domains, except for physical and role functioning. QoL was significantly associated with ES (P < 0.05) but not with objective results. Conclusions Achalasia is associated with severe QoL impairment. Following POEM, a significant and clinically relevant QoL improvement is observed. QoL is associated with ES, but not with objective results after POEM

Treatment of malignant gastric outlet obstruction with stents: An evaluation of the reported variables for clinical outcome

<p>Abstract</p> <p>Background</p> <p>Malignant gastric outlet obstruction (GOO) is commonly seen in patients with advanced gastric-, pancreatic-, duodenal, hepatobiliary or metastatic malignancies. Ten to 25% of patients with pancreatic cancer will develop duodenal obstruction during the course of the disease. Duodenal stenting with self-expandable metal stents is an alternative treatment to surgical bypass procedures. Our aim was to review the published literature regarding treatment of malignant GOO with stents to reveal whether the information provided is sufficient to evaluate the clinical effects of this treatment</p> <p>Methods</p> <p>A literature search from 2000 – 2007 was conducted in Pub Med, Embase, and Cochrane library, combining the following search terms: duodenal stent, malignant duodenal obstruction, gastric outlet obstruction, SEMS, and gastroenteroanastomosis.</p> <p>All publications presenting data with ≥ 15 patients and only articles written in English were included and a review focusing on the following parameters were conducted: 1) The use of graded scoring systems evaluating clinical success; 2) Assessment of Quality of life (QoL) before and after treatment; 3) Information on stent-patency; 4) The use of objective criteria to evaluate the stent effect.</p> <p>Results</p> <p>41 original papers in English were found; no RCT's. 16 out of 41 studies used some sort of graded scoring system. No studies had objectively evaluated QoL before or after stent treatment, using standardized QoL-questionnaires, 32/41 studies reported on stent patency and 9/41 performed an oral contrast examination after stent placement. Objective quantitative tests of gastric emptying had not been performed.</p> <p>Conclusion</p> <p>Available reports do not provide sufficient relevant information of the clinical outcome of duodenal stenting. In future studies, these relevant issues should be addressed to allow improved evaluation of the effect of stent treatment.</p

Snail regulates BMP and TGF beta pathways to control the differentiation status of glioma-initiating cells

Glioblastoma multiforme is a brain malignancy characterized by high heterogeneity, invasiveness, and resistance to current therapies, attributes related to the occurrence of glioma stem cells (GSCs). Transforming growth factor beta (TGF beta) promotes self-renewal and bone morphogenetic protein (BMP) induces differentiation of GSCs. BMP7 induces the transcription factor Snail to promote astrocytic differentiation in GSCs and suppress tumor growth in vivo. We demonstrate that Snail represses stemness in GSCs. Snail interacts with SMAD signaling mediators, generates a positive feedback loop of BMP signaling and transcriptionally represses the TGFB1 gene, decreasing TGF beta 1 signaling activity. Exogenous TGF beta 1 counteracts Snail function in vitro, and in vivo promotes proliferation and re-expression of Nestin, confirming the importance of TGFB1 gene repression by Snail. In conclusion, novel insight highlights mechanisms whereby Snail differentially regulates the activity of the opposing BMP and TGF beta pathways, thus promoting an astrocytic fate switch and repressing stemness in GSCs.Andra och tredje författare delar andra författarskapet.</p