Sublingual sufentanil for postoperative pain relief: first clinical experiences.

BACKGROUND: The sublingual sufentanil tablet system (SSTS) is a novel hand-held patient-controlled analgesia device developed for treatment of moderate-to-severe postoperative pain. Here we present the first results of its clinical use. METHODS: Adult patients undergoing major surgery in five hospitals in the Netherlands received the SSTS for postoperative pain relief as part of multimodal pain management that further included paracetamol and a nonsteroidal anti-inflammatory drug (NSAID). The following variables were collected: postoperative pain scores using the 11-point numerical rating score (NRS) at rest, number of tablets used, occurrence of nausea, and patient satisfaction scores. RESULTS: We included 280 patients in the study; the majority underwent laparoscopic abdominal (49%) or orthopedic (knee replacement) surgery (34%). The median NRS was 3.5 (interquartile range 2.3-4.0) on the day of surgery, 3.3 (2.3-4.0) on the first postoperative day, and 2.8 (2.0-4.0) on the second postoperative day; pain scores did not differ between surgery types. Mean number of tablets used was 19 (range 0-86). Nausea occurred in 34% of patients, more often in women (45% vs 19%). Overall satisfaction was high in 73% of patients. Satisfaction was correlated with pain relief (p<0.001) and inversely correlated with occurrence of nausea (p=0.01). DISCUSSION: In this data set obtained under real-life conditions we show that the SSTS effectively managed postoperative pain in abdominal and orthopedic surgeries. Future studies should determine patient populations that benefit most from the SSTS, assess the added values versus intravenous patient-controlled analgesia, and determine the pharmacoeconomics of the system.

MicroRNA signatures in chemotherapy resistant esophageal cancer cell lines.

AIM: To investigate expression of microRNA (miRNA) and potential targets in chemotherapy resistant esophageal cancer cell lines. METHODS: An in-vitro model of acquired chemotherapy resistance in esophageal adeno- (EAC) and squamous cell carcinoma (ESCC) cells was used, and microRNA expression profiles for cisplatin or 5-fluorouracil (5-FU) resistant variants vs chemotherapy sensitive controls were compared using microarray and quantitative real-time polymerase chain reaction (PCR). The expression of chemotherapy-relevant genes potentially targeted by the dysregulated microRNAs in the chemotherapy resistant variants was also evaluated. RESULTS: Chemotherapy resistant sublines were found to have specific miRNA signatures, and these miRNA signatures were different for the cisplatin vs 5-FU resistant cells from the same tumor cell line, and also for EAC vs ESCC cells with resistance to the same specific chemotherapy agent. Amongst others, miR-27b-3p, miR-193b-3p, miR-192-5p, miR-378 a-3p, miR-125a-5p and miR-18a-3p were dysregulated, consistent with negative posttranscriptional control of KRAS, TYMS, ABCC3, CBL-B and ERBB2 expression via these miRNAs. CONCLUSION: The current study supports the hypothesis that microRNA expression has an impact on chemotherapy resistance in esophageal cancer.

Argon plasma coagulation ablation versus endoscopic surveillance of Barrett's esophagus: late outcomes from two randomized trials.

BACKGROUND AND STUDY AIM: Argon plasma coagulation (APC) has been used to ablate dysplastic and nondysplastic Barrett's esophagus. We determined the longer-term efficacy of APC ablation within two randomized controlled trials of APC versus surveillance for Barrett's esophagus in patients in whom gastroesophageal reflux was controlled by either surgery or proton pump inhibitors. PATIENTS AND METHODS: 129 patients (surgical trial 70, medical trial 59) with Barrett's esophagus (nondysplastic or low grade dysplasia) were randomly allocated to either ablation using APC or to continuing endoscopy surveillance. Outcomes were determined at three time points: short-term (12 months), mid-term (42-75 months) and long-term (> 84 months). RESULTS: In the APC groups, initial ablation of > 95 % of the Barrett's esophagus was achieved in 61 of 63 patients; the > 95 % ablation persisted in 47 of 56 patients at short-term follow-up, in 33 of 49 at mid-term and in 21 of 32 at long-term follow-up. In the surveillance groups, the length of Barrett's esophagus reduced from a mean of 4.2 cm to 2.7 cm at long-term follow-up. High grade dysplasia (HGD) developed in 1 patient in the APC groups and in 3 in the surveillance groups. Low grade dysplasia developed in 1 APC patient and in 6 surveillance patients. CONCLUSIONS: APC ablation reduced the extent of Barrett's esophagus, and this reduction was maintained in some patients at longer-term follow-up. However, progression to HGD can still occur despite APC ablation, suggesting endoscopic surveillance is still required. CLINICAL TRIAL REGISTRATION: ACTRN012607000293460 and ACTRN12607000292471 (Australian Clinical Trials Registry).