Adenocarcinoma of the pancreas: the rationale for neoadjuvant therapy

The survival of patients with pancreatic cancer is dismal: tumor's resection is possible in only 10-20% of patients. This has prompted clinical studies with chemotherapy and/or radiotherapy designed to increase the number of patients eligible for surgery, to maximize local tumor control and to improve the length of survival. Since postoperative chemoradiation is often delayed in these patients due to morbidity and prolonged recovery time associated with surgery, investigators are assessing the efficacy of chemoradiation before pancreatic resection in patients with potentially resectable pancreatic carcinoma or the potential to downstage locally advanced pancreatic cancer to resectable tumor. The analysis of several clinical trials published so far shows that results are conflicting and not definitive. No randomized clinical studies have been reported. Moreover, neoadjuvant therapy rarely leads to surgical downstaging allowing for potentially curative pancreatic resections. Novel multimodality approaches are required, and patients should be entered on clinical, controlled trials

Antiepileptic drug discontinuation by people with epilepsy in the general population

Objective: Rate, reasons, and predictors of antiepileptic drug (AED) discontinuation were investigated in a well-defined cohort of people with epilepsy to verify efficacy and tolerability of treatment up to 20 years from treatment initiation. Methods: The history of AED usage in children and adults with epilepsy registered with 123 family physicians in an area of Northern Italy between 2000 and 2008 was recorded. Cumulative probabilities of AED withdrawal for specific reasons were estimated using cumulative incidence functions. The probabilities of withdrawing for terminal remission, and of achieving sustained remission while still on treatment, were also evaluated. The roles of sex, age at diagnosis, seizure types, duration at diagnosis, and syndrome were assessed with hazard ratios and 95% confidence intervals. Results: Seven hundred thirty-one of 747 individuals were treated with one or more AEDs during the disease course. The three commonest drugs were valproate, carbamazepine, and phenobarbital. Reported reasons for AED withdrawal were, in decreasing order, terminal remission, ineffectiveness, and adverse events. The probability of withdrawing the first AED for terminal remission was 1.0% at 1 year and increased to 20.0% at 20 years. Corresponding rates were 2.9% and 12.6% for ineffectiveness and 0.5% and 3.3% for adverse events. Reasons for withdrawal varied with individuals' age, sex, disease characteristics, and drugs. Significance: The initial AED given was retained in the majority of cases. Terminal remission, lack of efficacy, and adverse effects were, in decreasing order, the commonest reasons for AED discontinuation. Withdrawal could be predicted by age at diagnosis, sex, and clinical characteristics and varies among drugs

Long-term prognosis of epilepsy, prognostic patterns and drug resistance : a population-based study

Background and purpose: Seizures in most people with epilepsy remit but prognostic markers are poorly understood. There is also little information on the long-term outcome of people who fail to achieve seizure control despite the use of two antiepileptic drugs (drug resistance). Methods: People with a validated diagnosis of epilepsy in whom two antiepileptic drugs had failed were identified from primary care records. All were registered with one of 123 family physicians in an area of northern Italy. Remission (uninterrupted seizure freedom lasting 2 years or longer) and prognostic patterns (early remission, late remission, remission followed by relapse, no remission) were determined. Results: In all, 747 individuals (381 men), aged 11 months to 94 years, were followed for 11 045.5 person-years. 428 (59%) were seizure-free. The probability of achieving 2-year remission was 18% at treatment start, 34% at 2 years, 45% at 5, 52% at 10 and 67% at 20 years (terminal remission, 60%). Epilepsy syndrome and drug resistance were the only independent predictors of 2- and 5-year remission. Early remission was seen in 101 people (19%), late remission in 175 (33%), remission followed by relapse in 85 (16%) and no remission in 166 (32%). Treatment response was the only variable associated with differing prognostic patterns. Conclusion: The long-term prognosis of epilepsy is favourable in most cases. Early seizure remission is not invariably followed by terminal remission and seizure outcome varies according to well-defined patterns. Prolonged seizure remission and prognostic patterns can be predicted by broad syndromic categories and the failure of two antiepileptic drugs