Stendergrant4789

On neurological examination, no tremor or bradykinesia was observed; deep tendon reflexes, sensory examination, and strength were normal and preserved. Laboratory tests, neuroimaging, and electromyography were within normal. Topiramate was discontinued in all of the subjects. Full recovery was obtained in all cases. Conclusions To the authors' knowledge, there are 6 cases of myoclonus, 5 RLS, 2 dystonia, 1 dyskinesia, and 1 periodic limb MD. The best management is probably the discontinuation of TPM, but in RLS patients, the addition of a dopaminergic agonist can be beneficial.Purpose of review Clinical-trial design, analysis, and interpretation entails the use of efficient and reliable endpoints. Statistical issues related to endpoints warrant continued attention, as they may have a substantial impact on the conduct of clinical trials and on interpretation of their results. Recent findings We review concepts and discuss recent developments related to the use of time-to-event endpoints in studies on adjuvant and neoadjuvant therapy for colon, pancreatic, and gastric adenocarcinomas. The definition of endpoints has varied to a considerable extent in these settings. Although these variations are relevant in interpreting results from individual trials, they probably have a small impact when considered in aggregate. In terms of surrogacy, most published reports so far have used aggregated data. A few studies based on the preferred method of a metaanalysis of individual-patient data have shown that disease-free survival (DFS) is a surrogate for overall survival in the adjuvant therapy of stage III colon cancer and in gastric cancer, whereas DFS with a landmark of six months is a surrogate for overall survival in the neoadjuvant therapy of adenocarcinoma of the esophagus, gastroesophageal junction, or stomach. Summary Testing novel agents in gastrointestinal cancer requires continued attention to statistical issues related to endpoints.Purpose of review The value of adjuvant chemotherapy in rectal cancer is controversial with opinions varying from 'not be used' since randomized trials have not shown significant gains to 'be used as in colon cancer' as the need is the same and colon and rectal cancers are quite similar. This review will look upon data critically and with open eyes. Recent findings With the exception of one randomized phase II trial (ADORE) revealing a significant gain in disease-free survival using one more effective regimen (mFOLFOX) than bolus 5-fluorouracil leucovorin, no new data have been presented. However, bringing up aspects in previous trials, either considered irrelevant for the present situation or overall negative, of what adjuvant treatment can achieve, a small reduction (hazard ratio about 0.8) in the risk of recurrence is present. This reduction is not fundamentally different from that in colon cancer considering that adjuvant treatment for rectal cancer cannot be initiated as rapidly as it can after a colon cancer diagnosis. Summary Adjuvant chemotherapy after rectal cancer surgery reduces recurrence risks but the benefit is limited and for most patients not clinically relevant. Neoadjuvant therapy can be more effective but results from randomized trials are not yet available.Purpose of review This article will review the results of recent studies, which have investigated the duration of adjuvant chemotherapy and also suggest, which aspects of adjuvant treatment need investigation in future studies. Recent findings The IDEA collaboration investigated whether the duration of adjuvant chemotherapy with an oxaliplatin doublet could be reduced from 6 to 3 months. Although this study did not demonstrate noninferiority for 3 months treatment, it did show noninferiority for patients receiving 3 months CAPOX chemotherapy and for those patients with low-risk stage III disease receiving 3 months' treatment. There was also significantly less toxicity seen with 3 months' treatment. Recent studies have shown that detectable ctDNA postoperatively can predict those patients most likely to relapse and so benefit from adjuvant treatment. Summary It has been shown that for patients receiving adjuvant CAPOX chemotherapy, or those receiving adjuvant chemotherapy for low-risk stage III colon 3 months' chemotherapy gives similar outcomes to 6 months' treatment with significantly less toxicity.Purpose of review Biliary tract cancers (BTCs) have a poor prognosis; most patients present with advanced disease and, even after surgical resection for early-stage disease local and distant relapses are frequent. Involved resection margins and lymph node involvement are the most relevant known adverse prognostic factors. Historically clinicians have made clinical decisions based on data from institutional series and uncontrolled studies, with their inherent limitations. In this review, data from recently-reported prospective randomized trials are reviewed and clinical implications discussed. Recent findings Results from prospective randomized phase III trials (namely BILCAP, PRODIGE-12, and BCAT) are reviewed none of the studies met their primary endpoint by intention-to-treat analysis. However, following a per-protocol sensitivity analysis of the BILCAP study, adjuvant capecitabine (for 6 months) showed a clinically-relevant improvement in overall survival and provides reference data for future clinical trials. Summary Adjuvant chemotherapy with capecitabine should be considered following curative resection of BTC. Identification of benefit in anatomical subgroups is ongoing and future trials should also consider the implication of molecular subtypes of BTC (for prognostic impact and on-target therapeutic options).Purpose of review The modalities of management of resectable pancreatic ductal adenocarcinoma (PDAC) have evolved in recent years with new practice guidelines on adjuvant chemotherapy and results of randomized phase III trials. The aim of this review is to describe the state of the art in this setting and to highlight future possible perspectives. Recent findings Resectable PDAC is the tumor without vascular contact or a limited venous contact without vein irregularity. Several pathologic and biologic robust prognostic factors such as an R0 resection defined by a margin at least 1 mm have been validated. In phase III trials, the doublet gemcitabine-capecitabine provided a statistically significant, albeit modest overall survival benefit, but failed to show an improvement in relapse-free survival. Similarly, gemcitabine plus nab-paclitaxel did not increase disease-free survival. RNA Synthesis inhibitor Modified FOLFIRINOX led to improved disease-free survival, overall survival, and metastasis-free survival, with acceptable toxicity. In the future, prognostic and/or predictive biomarkers could lead the optimization of therapeutic strategies and neoadjuvant treatment could become a standard of care in PDAC.