Combination of diclofenac plus somatostatin in the prevention of post-ERCP pancreatitis: a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND STUDY AIMS: Pancreatitis is the most common complication of therapeutic endoscopic retrograde cholangiopancreatography (ERCP), and many pharmacoprophylactic approaches have been suggested, though not without controversy. The aim was to investigate the impact of combined therapy with diclofenac plus somatostatin on reducing the frequency and severity of post-ERCP pancreatitis (PEP). PATIENTS AND METHODS: A prospective, double-blind, placebo-controlled trial was conducted in two tertiary referral centers, with 540 eligible patients randomized to receive either combined therapy with diclofenac 100 mg rectally 30 to 60 minutes before ERCP plus somatostatin 0.25 mg/h for 6 hours (group A), or a placebo suppository identical in appearance to the diclofenac along with saline solution (group B). Patients were clinically evaluated and serum amylase levels were determined before ERCP and at 6 and 24 hours post-procedure. Standardized criteria were used to diagnose and grade the severity of PEP. Adverse events were recorded prospectively. RESULTS: There were no statistical differences between the groups regarding demographic data, ERCP findings, and procedure risk factors for PEP. The overall incidence of acute pancreatitis was 7.2 %. The PEP rate was significantly lower in the patients who received the combination therapy than in controls (4.7 % vs. 10.4 %, P = 0.015). Previous history of acute pancreatitis (P = 0.001), pancreatic opacification of first-class branches and beyond (P = 0.008), and absence of pharmacoprophylaxis (P = 0.023) were identified as independent risk factors for PEP in multivariate analysis. CONCLUSION: Although combined prophylactic therapy with diclofenac plus somatostatin was promising in reducing frequency of PEP, further comparative large-scale studies are needed to confirm our findings before definitive conclusions can be drawn.

Front-line paclitaxel and topotecan chemotherapy in advanced or metastatic non-small-cell lung cancer: a phase II trial.

PURPOSE: Based on previous experience, we combined topotecan with paclitaxel (weekly administration) in patients with non-small-cell lung cancer (NSCLC). Our primary objective was to determine the response rate and survival and our secondary objective, the safety of the regimen. METHODS: From October 2003, until March 2005, 45 patients all with histologically or cytologically confirmed NSCLC were enrolled. All patients were chemotherapy and radiotherapy naive. Both agents were infused on day 1 of every week once for three consecutive weeks, every 28 days. Three infusions were considered as one course. The treatment plan was to give three courses (nine infusions) and then to evaluate the response. Topotecan (1.75 mg/m2) was infused for 30 min and paclitaxel (70 mg/m2) for 90 min; these doses had been established as the maximum tolerated dose in a previous phase I-II trial. RESULTS: Eighteen/45 (40%) patients responded, 2 (4.4%) complete responses and 16 (35.6%) partial responses. Twenty-one (46.7%) patients had stable disease, and 6 (13.3%) disease progression. The median duration of response was 8 months and median time to tumor progression 9 months. Grade 3 and 4 neutropenia was observed in two patients (in these two patients, the dose of both drugs was reduced by 25% and G-CSF was given), grade 4 thrombocytopenia in one patient and grade 4 anemia in one patient. CONCLUSION: This novel combination of topotecan-paclitaxel in a weekly administration rendered a 40% response rate, with very low toxicity in stages IIIA, IIIB and IV NSCLC patients.

Amyloid PET and MRI in Alzheimer's disease and mild cognitive impairment.

The neurodegenerative disorder Alzheimer's disease (AD) is the most common form of dementia. It is characterized by progressive impairment of cognitive functions and behavior. To distinguish clinically AD from other forms of dementia is an ongoing challenge. In addition, although mild cognitive impairment (MCI) is recognized as a risk factor for dementia, it remains a challenge to predict on an individual level who will convert to become demented. Amyloid beta (Abeta) is one of the crucial pathological findings in AD. Recently, amyloid tracers for PET imaging have been developed successfully which may offer the unique possibility for measuring fibrillar Abeta load in the living brain. Therefore, in the near future positron emission tomography (PET) may become an important tool for in vivo amyloid imaging contributing to early (differential) diagnosis as well as evaluation of treatment response in AD. Moreover, Abeta may play a role in prediction the conversion of MCI to AD. In this paper we review the recent development of the molecular imaging technique PET and its different radiopharmaceuticals on the trail for imaging amyloid in AD and the conversion of MCI to AD.

Efficacy of long-term lamivudine monotherapy in patients with hepatitis B e antigen-negative chronic hepatitis B.

We evaluated the safety and efficacy of long-term lamivudine monotherapy in a group of 25 patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. Lamivudine was administered in a daily dose of 150 mg for a mean of 26 +/- 7 months and was well tolerated. No patient lost hepatitis B surface antigen (HBsAg). The rate of initial biochemical response increased from 88% at 6 months to 96% at 12 months of therapy, but it progressively decreased thereafter; the biochemical remission rate was 68% at 18 months, 59. 5% at 24 months, and 42.5% at >/=30 months. Alanine transaminase (ALT) increased to higher than the baseline levels in 8 of the 11 patients with a biochemical breakthrough reaching acute hepatitis levels in 6 of them. Acute icteric hepatitis developed in one patient. The virologic remission rate assessed by a sensitive quantitative polymerase chain reaction (PCR) assay was 68% at both 6 and 12 months, decreasing thereafter to 52% at 18 months and to 41. 6% at both 24 and >/=30 months. Virologic breakthroughs were always persistent and preceded ALT elevations by a median of 4 (3-24) months. YMDD mutants were detected in all patients with a virologic breakthrough. In conclusion, in patients with HBeAg-negative chronic hepatitis B, long-term lamivudine therapy is safe and is associated with high biochemical and virologic response rates at the end of the first year. However, response rates tend to decrease with time and breakthroughs due to YMDD mutants accumulate. ALT activity during breakthroughs often exceeds the baseline and may reach even acute hepatitis levels.