Acute cholecystitis - a cohort study in a real-world clinical setting (REWO study, NCT02796443).

BACKGROUND: For decades, the optimal timing of surgery for acute cholecystitis has been controversial. Recent meta-analyses and population-based studies favor early surgery. One recent large randomized trial has demonstrated that a delayed approach increases morbidity and cost compared to early surgery within 24 hours of hospital admission. Since cases of severe cholecystitis were excluded from this trial, we argue that these results do not reflect real-world clinical situations. From our point of view, these results were in contrast to the clinical experience with our patients; so, we decided to analyze critically all our patients with the null hypothesis that the patients treated with a delayed cholecystectomy after an acute cholecystitis have a similar or even better outcome than those treated with an early operative approach. PATIENTS AND METHODS: We retrospectively analyzed clinical data from all patients with cholecystectomies in the period between January 2006 and September 2015. A total of 1,723 patients were categorized into four groups: early (n=138): urgent surgery of patients with acute cholecystitis within the first 72 hours of the onset of symptoms; intermediate (n=297): surgery of patients with acute cholecystitis within an average of 10 days after the onset of symptoms; delayed (n=427): initial non-surgical treatment of acute cholecystitis with surgery performed within 6-12 weeks of the onset of symptoms; and elective (n=868): cholecystectomy within a symptom-free interval of choice in patients with symptomatic cholecystolithiasis without signs of acute cholecystitis. RESULTS: In a real-world scenario, early/intermediate cholecystectomy in acute cholecystitis was associated with a significant increase in morbidity and mortality (Clavien-Dindo score) compared to a delayed approach with surgery performed 6-12 weeks after the onset of symptoms. The adjusted linear rank statistics showed a decrease in the complication score with values of 2.29 in the early group, 0.48 in the intermediate group, -0.26 in the delayed group and -2.12 in the elective group. The results translate into a continuous decrease of the complication score from early over intermediate and delayed to the elective group. CONCLUSION: These results demonstrate that delayed cholecystectomy can be performed safely. In cases with severe cholecystitis, early and/or intermediate approaches still have a relatively high risk of morbidity and mortality.

2D vs. 3D imaging in laparoscopic surgery-results of a prospective randomized trial.

PURPOSE: 3D imaging is an upcoming technology in laparoscopic surgery, and recent studies have shown that the modern 3D technique is superior in an experimental setting. However, the first randomized controlled clinical trial in this context dates back to 1998 and showed no significant difference between 2D and 3D visualization using the first 3D generation technique, which is now more than 15 years old. METHODS: Positive results measured in an experimental setting considering 3D imaging on surgical performance led us to initiate a randomized controlled pragmatic clinical trial to validate our findings in daily clinical routine. Standard laparoscopic operations (cholecystectomy, appendectomy) were preoperatively randomized to a 2D or 3D imaging system. We used a surgical comfort scale (Likert scale) and the Raw NASA Workload TLX for the subjective assessment of 2D and 3D imaging; the duration of surgery was also measured. RESULTS: The results of 3D imaging were statistically significant better than 2D imaging concerning the parameters "own felt safety" and "task efficiency"; the difficulty level of the procedures in the 2D and 3D groups did not differ. Overall, the Raw NASA Workload TLX showed no significance between the groups. CONCLUSION: 3D imaging could be a possible advantage in laparoscopic surgery. The results of our clinical trial show increased personal felt safety and efficiency of the surgeon using a 3D imaging system. Overall of the procedures, the findings assessed using Likert scales in terms of own felt safety and task efficiency were statistically significant for 3D imaging. The individually perceived workload assessed with the Raw NASA TLX shows no difference. Although these findings are subjective impressions of the performing surgeons without a clear benefit for 3D technology in clinical outcome, we think that these results show the capability that 3D laparoscopy can have a positive impact while performing laparoscopic procedures.

Laparoscopic surgery: A qualified systematic review.

AIM: To review current applications of the laparoscopic surgery while highlighting the standard procedures across different fields. METHODS: A comprehensive search was undertaken using the PubMed Advanced Search Builder. A total of 321 articles were found in this search. The following criteria had to be met for the publication to be selected: Review article, randomized controlled trials, or meta-analyses discussing the subject of laparoscopic surgery. In addition, publications were hand-searched in the Cochrane database and the high-impact journals. A total of 82 of the findings were included according to matching the inclusion criteria. Overall, 403 full-text articles were reviewed. Of these, 218 were excluded due to not matching the inclusion criteria. RESULTS: A total of 185 relevant articles were identified matching the search criteria for an overview of the current literature on the laparoscopic surgery. Articles covered the period from the first laparoscopic application through its tremendous advancement over the last several years. Overall, the biggest advantage of the procedure has been minimizing trauma to the abdominal wall compared with open surgery. In the case of cholecystectomy, fundoplication, and adrenalectomy, the procedure has become the gold standard without being proven as a superior technique over the open surgery in randomized controlled trials. Faster recovery, reduced hospital stay, and a quicker return to normal activities are the most evident advantages of the laparoscopic surgery. Positive outcomes, efficiency, a lower rate of wound infections, and reduction in the perioperative morbidity of minimally invasive procedures have been shown in most indications. CONCLUSION: Improvements in surgical training and developments in instruments, imaging, and surgical techniques have greatly increased safety and feasibility of the laparoscopic surgical procedures.

Margatoxin inhibits VEGF-induced hyperpolarization, proliferation and nitric oxide production of human endothelial cells.

BACKGROUND: Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells (EC) in vitro and angiogenesis in vivo. Furthermore, a role of VEGF in K(+) channel, nitric oxide (NO) and Ca(2+) signaling was reported. We examined whether the K(+) channel blocker margatoxin (MTX) influences VEGF-induced signaling in human EC. METHODS: Fluorescence imaging was used to analyze changes in the membrane potential (DiBAC), intracellular Ca(2+) (FURA-2) and NO (DAF) levels in cultured human EC derived from human umbilical vein EC (HUVEC). Proliferation of HUVEC was examined by cell counts (CC) and [(3)H]-thymidine incorporation (TI). RESULTS: VEGF (5--50 ng/ml) caused a dose-dependent hyperpolarization of EC, with a maximum at 30 ng/ml (n=30, p<0.05). This effect was completely blocked by MTX (5 micromol/l). VEGF caused an increase in transmembrane Ca(2+) influx (n=30, p<0.05) that was sensitive to MTX and the blocker of transmembrane Ca(2+) entry 2-aminoethoxydiphenyl borate (APB, 100 micromol/l). VEGF-induced NO production was significantly reduced by MTX, APB and a reduction in extracellular Ca(2+) (n=30, p<0.05). HUVEC proliferation, examined by CC and TI, was significantly increased by VEGF and inhibited by MTX (CC: -58%, TI --121%); APB (CC --99%, TI--187%); N-monomethyl-L-arginine (300 micromol/l: CC: -86%, TI --164%). CONCLUSIONS: VEGF caused an MTX-sensitive hyperpolarization which results in an increased transmembrane Ca(2+) entry that is responsible for the effects on endothelial proliferation and NO production.