Prophylactic 5-Fr pancreatic duct stents are superior to 3-Fr stents: a randomized controlled trial.

BACKGROUND: Temporary prophylactic pancreatic duct stenting effectively reduces post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk patients, but the optimal stent remains unclear. We compared rate of spontaneous passage, and technical difficulty of placement for 3-Fr and 5-Fr stents. METHODS: A randomized controlled trial at a single academic medical center. Patients deemed high risk for PEP randomly received 5-Fr or 3-Fr pancreatic duct stents. Primary outcome was spontaneous stent passage by 2 weeks. Secondary outcomes were ease and time for stent placement, and number of guide wires required for the entire procedure. RESULTS: Patients (69 female [89 %]; mean age 44.9 years, standard deviation [SD] 16.8) were randomly assigned to receive 5-Fr (n = 38) and 3-Fr (n = 40) stents. Indications for stenting were similar. Seven patients in the 3-Fr group actually received a 5-Fr stent, and two in the 5-Fr group had a 3-Fr stent. Spontaneous passage or non-passage was confirmed in 64 (83 %). No statistically significant difference in spontaneous passage rates was seen (5-Fr group, 68.4 %; 3-Fr group 75.0 %; P = 0.617). Non-passage rates were 10.5 % (5-Fr group) and 10.0 % (3-Fr group) ( P = 1.00). The study was stopped after a futility analysis for the primary end point. Placement of 5-Fr stents was rated easier, at a mean score of 1.8 (5-Fr) vs. 3.4 (3-Fr), P < 0.001, with a trend towards being faster, 9.2 vs. 11.1 minutes ( P = 0.355). Fewer guide wires were required for 5-Fr stent placement, 1.5 vs. 1.9 ( P = 0.002). PEP rates did not differ ( P = 0.519). CONCLUSION: Placement of 5-Fr compared to 3-Fr pancreatic duct stents for PEP prophylaxis is easier, faster, and requires fewer wires. No statistically significant difference in spontaneous passage was found between the two sizes.

Oesophageal hypersensitivity is associated with features of psychiatric disorders and the irritable bowel syndrome.

BACKGROUND: Twenty per cent of patients with heartburn do not respond to proton pump inhibitors (PPIs). Many have normal oesophageal acid exposure. We hypothesized that such PPI non-responders have heightened oesophageal sensation, and that oesophageal hypersensitivity is associated with psychiatric features including somatization and anxiety. AIM: To compare oesophageal sensation in subjects with heartburn categorized by response to PPI, and to correlate oesophageal sensation with psychiatric features. METHODS: Twenty-one PPI responders, nine PPI non-responders and 20 healthy volunteers completed questionnaires of psychiatric disorders and gastrointestinal symptoms. Subjects underwent oesophageal sensory testing with acid perfusion and balloon distension. RESULTS: Healthy volunteers displayed higher thresholds for sensation and discomfort from balloon distension than heartburn subjects (sensation P = 0.04, discomfort P = 0.14). Psychiatric disorders were associated with increased intensity of sensation (P = 0.02) and discomfort from acid (P = 0.01). Somatization was associated with increased discomfort from balloon distension (P = 0.006). Features of irritable bowel syndrome were associated with increased sensation and discomfort. CONCLUSIONS: Heartburn subjects tend to have heightened oesophageal sensation, suggesting that oesophageal hypersensitivity may persist despite therapy with PPI. Oesophageal hypersensitivity is associated with features of psychiatric disease and with the irritable bowel syndrome, which might partly explain the aetiology of heartburn symptoms that are refractory to PPI.

Oxygen-mediated regulation of skeletal muscle satellite cell proliferation and adipogenesis in culture.

Major problems in stem cell biology revolve around defining the developmental potential of cell populations and understanding how their potential is maintained or progressively restricted. Oxygen (O(2)) is an obvious environmental factor which has received little attention in culturing skeletal muscle progenitor cells. In this work, we examine the effects of O(2) levels on the developmental potential, proliferative capacity, and phenotype of the adult skeletal muscle fiber progenitor population (satellite cells), and cell lines that model multipotential embryonic paraxial mesoderm from which skeletal muscle develops. Both satellite cell proliferation and survival of mature fibers increased in physiologic (6%) O(2) vs. non-physiologic 20% O(2) used in virtually all traditional cell culture. Six percent O(2) conditions also accelerated the up-regulation of multiple MyoD family myogenic regulatory factors (MRFs). An unexpected finding was that fiber-adherent satellite cells could assume a non-myogenic phenotype. By the criteria of molecular markers and gross lipid accumulation, satellite cells were found to assume an adipocyte phenotype, and did so more prominently in 20% O(2) than in physiologic O(2). Selection of the adipogenic fate and execution of adipogenesis by multipotential mesenchymal cell lines was also dramatically higher in traditional 20 vs. 6% O(2), and decreased adipogenesis in physiologic O(2) was associated with significantly less expression of the adipogenic regulator, PPAR gamma. These results suggest that regulatory pathways affected by O(2) are important for satellite cell proliferation, execution of cell fate, and parent muscle survival in culture, and so may play a role in vivo under normal or pathologic conditions.