Background Levodopa is the most effective therapy for Parkinson's disease (PD), but chronic treatment is associated with the development of potentially disabling motor complications. Experimental studies suggest that motor complications are due to non-physiologic, intermittent administration of the drug, and can be reduced with continuous delivery. Levodopa-carbidopa intestinal gel (LCIG) is a form of levodopa that can be delivered continuously through an intrajejunal percutaneous tube. Methods We performed a 12-week double-blind, double-dummy, double-titration, multi-center trial to evaluate the efficacy and safety of LCIG compared to optimized, oral, immediate-release levodopa-carbidopa (LC-IR) in advanced PD patients with motor complications. The primary endpoint was change from baseline to final visit in motor “Off” time. Motor “On” time without troublesome dyskinesia was the key secondary endpoint. Findings 71 patients with advanced PD were randomized to receive continuous LCIG infusion plus placebo LC-IR capsules (n=37) or to receive LC-IR capsules plus continuous placebo LCIG infusion (n=34). Both groups were titrated to optimal effect. 93% of subjects (n=66) completed the trial. In comparison to LC-IR, LCIG significantly reduced “Off” time by a mean (±SE) of 1·91±0·57 hours (P=0·0015) and increased “On” time without troublesome dyskinesia by a mean of 1·86±0·65 hours (P=0·006). Adverse events were primarily related to the surgical procedure and the device, and while potentially serious, were not associated with residual deficit or mortality. Interpretation In comparison to standard oral LC-IR, LCIG significantly reduced “Off” time and increased “On” time without troublesome dyskinesia in patients with advanced PD. Adverse events were largely due to the procedure and the device. Benefits are of greater magnitude than have been obtained with medical therapies to date, and represent the first demonstration of the benefit of continuous levodopa delivery in a double-blind controlled study.

Abstract. Background-Short chain fatty acid (SCFA) deficiency is associated with colitis in animals and humans, and the mucosal metabolism of these compounds is decreased in ulcerative colitis. Aims-To assess the efficacy of topical SCFA treatment in ulcerative colitis. Patients and Methods-103 patients with distal ulcerative colitis were entered into a six week, double-blind, placebo controlled trial of rectal SCFA twice daily; patients who were unchanged on placebo were offered SCFA in an open-label extension trial. Results-Of the 91 patients completing the trial, more patients in the SCFA treated than in the placebo treated group improved (33% v 20%, p=0 14, NS). Those on SCFA also had larger, but statistically non-significant, reductions in every component of their clinical and histological activity scores. In patients with a relatively short current episode of colitis (<6 months, n=42), more responded to SCFA than to placebo (48% v 18%, p=003). These patients also had larger, but statistically non-significant, decreases in their clinical activity index (p=0.08 v placebo). Every patient who improved used at least five of six of the prescribed rectal SCFA irrigations, whereas only 37% who did not improve were as compliant. In the open-label extension trial, 65% improved on SCFA; these patients also had significant reductions (p<0.02) in their clinical and histological activity scores. Conclusions-Although SCFA enemas were not of therapeutic value in this controlled trial, the results suggest efficacy in subsets of patients with distal ulcerative colitis including those with short active episodes. Prolonged contact with rectal mucosa seems to be necessary for therapeutic benefit. (Gut 1997; 40: 485-491) Keywords: short chain fatty acids, distal ulcerative colitis.Treatment of distal ulcerative colitis consists mainly of topical or oral 5-aminosalicylic acid (5-ASA) compounds or corticosteroids, or both. These compounds alter the inflammatory response by decreasing oxygen free radical activity and proinflammatory cytokine release, and by modifying the lipo-and cyclooxygenase pathways of arachidonic acid metabolism.' They are relatively expensive, not uniformly effective, are not free of undesired systemic effects even in their new formula-

A BST RACT : Background: Levodopa-carbidopa intestinal gel (designated as carbidopa-levodopa enteral suspension in the United States) provides stable plasma levodopa concentrations and reduces motor fluctuations in advanced Parkinson's disease patients through continuous delivery of levodopa via percutaneous endoscopic gastrojejunostomy. We report long-term safety and efficacy outcomes from an open-label phase 3 treatment program. Methods: PD patients (n 5 262) who completed a 12-week double-blind study and its 52-week open-label extension or a separate 54-week open-label study were enrolled in this ongoing phase 3 open-label, multinational study (NCT00660673). Safety and efficacy assessments were collected every 6 months. Results: Mean total duration of exposure to levodopacarbidopa intestinal gel was 4.1 years (range, 1.2 to 6.9 years). The overall discontinuation rate was 34% (average annual discontinuation rate, 10%). Although most patients (94%) reported an adverse event, the rate of adverse events decreased over time; 53% experienced a serious adverse event. Of patients in this extension study, 54% required jejunal tube replacement during the study, and 37% required percutaneous endoscopic gastrostomy tube replacement. Most patients were on levodopa monotherapy. Patients maintained reductions in "off" time and increases in mean "on" time without dyskinesia from initial levodopa-carbidopa intestinal gel infusion to he study end point (P < 0.001; n 5 81). Activities of daily living and quality-of-life assessments demonstrated significant improvements that persisted through the study. Conclusions: This long-term study demonstrates sustained and clinically meaningful benefits from levodopacarbidopa intestinal gel in advanced PD patients.--

Levodopa–carbidopa intestinal gel (LCIG) delivered continuously via percutaneous endoscopic gastrojejunostomy (PEG-J) tube has been reported, mainly in small open-label studies, to significantly alleviate motor complications in Parkinson’s disease (PD). A prospective open-label, 54-week, international study of LCIG is ongoing in advanced PD patients experiencing motor fluctuations despite optimized pharmacologic therapy. Pre-planned interim analyses were conducted on all enrolled patients (n = 192) who had their PEG-J tube inserted at least 12 weeks before data cutoff (July 30, 2010). Outcomes include the 24-h patient diary of motor fluctuations, Unified Parkinson’s Disease Rating Scale (UPDRS), Clinical Global Impression-Improvement (CGI-I), Parkinson’s Disease Questionnaire (PDQ-39), and safety evaluations. Patients (average PD duration 12.4 yrs) were taking at least one PD medication at baseline. The mean (±SD) exposure to LCIG was 256.7 (±126.0) days. Baseline mean “Off” time was 6.7 h/day. “Off” time was reduced by a mean of 3.9 (±3.2) h/day and “On” time without troublesome dyskinesia was increased by 4.6 (±3.5) h/day at Week 12 compared to baseline. For the 168 patients (87.5%) reporting any adverse event (AE), the most common were abdominal pain (30.7%), complication of device insertion (21.4%), and procedural pain (17.7%). Serious AEs occurred in 60 (31.3%) patients. Twenty-four (12.5%) patients discontinued, including 14 (7.3%) due to AEs. Four (2.1%) patients died (none deemed related to LCIG). Interim results from this advanced PD cohort demonstrate that LCIG produced meaningful clinical improvements. LCIG was generally well-tolerated; however, device and procedural complications, while generally of mild severity, were common.

EUS staging of rectal cancer after chemoradiation is inaccurate, especially in the group of patients with visual and EUS evidence of response. Its routine use for staging purposes after neoadjuvant chemoradiation for rectal cancer should be discouraged.