Meta-analysis of randomized controlled trials and individual patient data comparing minimally invasive with open oesophagectomy for cancer.

BACKGROUND: Minimally invasive oesophagectomy (MIO) for oesophageal cancer may reduce surgical complications compared with open oesophagectomy. MIO is, however, technically challenging and may impair optimal oncological resection. The aim of the present study was to assess if MIO for cancer is beneficial. METHODS: A systematic literature search in MEDLINE, Web of Science and CENTRAL was performed and randomized controlled trials (RCTs) comparing MIO with open oesophagectomy were included in a meta-analysis. Survival was analysed using individual patient data. Random-effects model was used for pooled estimates of perioperative effects. RESULTS: Among 3219 articles, six RCTs were identified including 822 patients. Three-year overall survival (56 (95 per cent c.i. 49 to 62) per cent for MIO versus 52 (95 per cent c.i. 44 to 60) per cent for open; P = 0.54) and disease-free survival (54 (95 per cent c.i. 47 to 61) per cent versus 50 (95 per cent c.i. 42 to 58) per cent; P = 0.38) were comparable. Overall complication rate was lower for MIO (odds ratio 0.33 (95 per cent c.i. 0.20 to 0.53); P < 0.010) mainly due to fewer pulmonary complications (OR 0.44 (95 per cent c.i. 0.27 to 0.72); P < 0.010), including pneumonia (OR 0.41 (95 per cent c.i. 0.22 to 0.77); P < 0.010). CONCLUSION: MIO for cancer is associated with a lower risk of postoperative complications compared with open resection. Overall and disease-free survival are comparable for the two techniques. LAY SUMMARY: Oesophagectomy for cancer is associated with a high risk of complications. A minimally invasive approach might be less traumatic, leading to fewer complications and may also improve oncological outcome. A meta-analysis of randomized controlled trials comparing minimally invasive to open oesophagectomy was performed. The analysis showed that the minimally invasive approach led to fewer postoperative complications, in particular, fewer pulmonary complications. Survival after surgery was comparable for the two techniques.

Oesophagectomy for cancer is associated with a high risk of complications. A minimally invasive approach might be less traumatic, leading to fewer complications and may also improve oncological outcome. A meta-analysis of randomized controlled trials comparing minimally invasive to open oesophagectomy was performed. The analysis showed that the minimally invasive approach led to fewer postoperative complications, in particular, fewer pulmonary complications. Survival after surgery was comparable for the two techniques.

[Clinical evidence for metabolic surgery]. / Klinische Evidenz der metabolischen Chirurgie.

The metabolic effect of bariatric surgery is well-established and is considered to be self-evident in morbidly obese patients with a body mass index (BMI) > 40 kg/m(2). Metabolic surgery performed on patients with obesity grades II (BMI 35-40 kg/m(2)) and I (BMI 30-35 kg/m(2)) according to the World Health Organization (WHO) has increased in recent years; however, the indications for metabolic surgery in obesity grades I and II are currently under debate due to insufficient evidence. In the last 5 years several highly qualified randomized clinical trials have been published which evaluated the effect of metabolic surgery in patients with obesity grades I and II in comparison to conservative therapy. Based on these data the efficacy of metabolic surgery in short-term follow-up (12-36 months) is unquestionable when compared to conservative therapy according to the current guidelines. Besides improved glycemic control and remission of diabetes, metabolic surgery has the potential to have a positive influence on diabetic complications, such as diabetic retinopathy, nephropathy and polyneuropathy, as well as on comorbidities, such as arterial hypertension and dyslipidemia. Future clinical trials should address the long-term (> 36 months) effects of metabolic surgery, patient selection criteria and choice of procedure.

Polypropylene, polyester or polytetrafluoroethylene-is there an ideal material for mesh augmentation at the esophageal hiatus? Results from an experimental study in a porcine model.

PURPOSE: Knowledge about the influence of underlying biomaterial on behavior of surgical meshes at the esophageal hiatus is rare, but essential for safe and effective hiatal hernia surgery. This study aimed to characterize the influence of polymer material on mesh behavior at the hiatus. METHODS: 24 pigs in three groups of eight underwent implantation of either polypropylene (PP), polyester (PET) or polytetrafluoroethylene (PTFE) mesh placed circularly at the esophageal hiatus. After 8 weeks, necropsy and measurements were performed evaluating mesh deformation, adhesion formation, fixation of the esophagogastric junction and mesh position. Foreign body reaction was assessed by mononuclear cell count and immunostaining of Ki-67. Tissue integration was evaluated by immunostaining of type I and type III collagen fibers. RESULTS: Mesh shrinkage was the highest for PTFE, lower for PP and the lowest for PET (34.9 vs. 19.8 vs. 12.1 %; p = 0.002). Mesh aperture for the esophagus showed an enlargement within all groups, which was highest for PTFE compared to PP and PET (100.8 vs. 47.0 vs. 35.9 %; p = 0.001). The adhesion score was highest for PP, lower for PTFE and the lowest for PET (11.0 vs. 9.5 vs. 5.0; p = 0.001) and correlated positively with the score of esophagogastric fixation (r s = 0.784, p < 0.001). No mesh migration, erosion or stenosis of the esophagus occurred. Evaluation of foreign body reaction and tissue integration showed no significant differences. CONCLUSIONS: In this experimental setting, PP-meshes showed the most appropriate characteristics for augmentation at the hiatus. Due to solid fixation of the esophagogastric junction and low shrinkage tendency, PP-meshes may be effective in preventing hiatal hernia recurrence. The use of PTFE-mesh at the hiatus may be disadvantageous due to high shrinkage rates and correlating enlargement of the aperture for the esophagus.

Microwave ablation of porcine kidneys in vivo: effect of two different ablation modes ("temperature control" and "power control") on procedural outcome.

PURPOSE: This study was designed to analyze the effect of two different ablation modes ("temperature control" and "power control") of a microwave system on procedural outcome in porcine kidneys in vivo. METHODS: A commercially available microwave system (Avecure Microwave Generator; MedWaves, San Diego, CA) was used. The system offers the possibility to ablate with two different ablation modes: temperature control and power control. Thirty-two microwave ablations were performed in 16 kidneys of 8 pigs. In each animal, one kidney was ablated twice by applying temperature control (ablation duration set point at 60 s, ablation temperature set point at 96°C, automatic power set point; group I). The other kidney was ablated twice by applying power control (ablation duration set point at 60 s, ablation temperature set point at 96°C, ablation power set point at 24 W; group II). Procedural outcome was analyzed: (1) technical success (e.g., system failures, duration of the ablation cycle), and (2) ablation geometry (e.g., long axis diameter, short axis diameter, and circularity). RESULTS: System failures occurred in 0% in group I and 13% in group II. Duration of the ablation cycle was 60±0 s in group I and 102±21 s in group II. Long axis diameter was 20.3±4.6 mm in group I and 19.8±3.5 mm in group II (not significant (NS)). Short axis diameter was 10.3±2 mm in group I and 10.5±2.4 mm in group II (NS). Circularity was 0.5±0.1 in group I and 0.5±0.1 in group II (NS). CONCLUSIONS: Microwave ablations performed with temperature control showed fewer system failures and were finished faster. Both ablation modes demonstrated no significant differences with respect to ablation geometry.

Detection of three novel translocations and specific common chromosomal break sites in malignant melanoma by spectral karyotyping.

Chromosomal aberrations in malignant melanoma cells have been reported using standard chromosome banding analysis and comparative genomic hybridization. To identify marker chromosomes and translocations that are difficult to characterize by standard banding analysis, 15 early passage malignant melanoma cell lines were examined using spectral karyotyping. All 15 tumor cell lines had lost all or part of 1p and 10q. Losses of material on chromosome arms 4p (12/15), 6q (12/15), 9p (15/15), 12p (13/15), 12q (13/15), 13q (11/15), and 19q (14/15) were the next most frequent events. Gain of chromosome arms 1q (11/15), 6p (13/15), and 20q11 (14/15) was also observed. Interestingly, we identified translocations der(12)t(12;20)(q15;q11), der(19)t(10;19)(q23;q13), and der(12)t(12;19)(q13;q13) in 4/15 tumors. Three recurring translocations involving four of the most frequent break points were detected. The identification of recurring translocations and unique chromosome break points in melanoma will aid in the identification of the genes that are important in the neoplastic process.

The effects of age and lifestyle factors on the accumulation of cytogenetic damage as measured by chromosome painting.

Individual responses to the aging process are variable and are affected by genetic as well as environmental factors. Fluorescent in situ hybridization with whole chromosome probes ('chromosome painting') provides an efficient approach for detecting structural chromosome aberrations in human lymphocytes. This rapid and sensitive technique is an effective tool for quantifying chronic exposure to environmental agents which may result in an accumulation of cytogenetic damage with age. We have applied this technology to a normal, putatively unexposed, population to document the relationship between age and the accumulation of cytogenetic damage, as well as to establish a baseline frequency of stable aberrations. Using probes for chromosomes 1, 2 and 4 simultaneously, the equivalent of 1000 metaphases was scored for stable and unstable aberrations from each of 91 subjects ranging in age from newborns (umbilical cord bloods; n = 14) to adults aged 19 to 79 years. Each subject (or one parent of each newborn) completed an extensive questionnaire to identify possible lifestyle factors that may influence the frequency of cytogenetic damage. Our findings show a significant increase in stable aberrations (translocations and insertions) with age (p < 0.0001). We also observed age-related increases with dicentrics (p < 0.0001) and acentric fragments (p < 0.0001). Relative to the frequencies observed in cord bloods, the frequencies of stable aberrations, dicentrics, and acentric fragments in adults aged 50 and over were elevated 10.6-fold, 3.3-fold, and 2.9-fold, respectively. Nine variables other than age are significantly associated with the frequency of stable aberrations; these are: smoking (two variables), consumption of diet drinks and/or diet sweeteners (4 variables), exposure to asbestos or coal products (1 variable each), and having a previous major illness (1 variable). Newborns whose mothers smoked during pregnancy had a 1.5-fold increase in stable aberrations (p = 0.029). Repeat samples from a subset of the adults indicate that for most subjects there is little change in individual translocation frequencies over a period of two to three years. These results support the hypothesis that stable chromosome aberrations show a greater accumulation with age than do unstable aberrations and suggest that lifestyle factors contribute to the accumulation of cytogenetic damage.

Analysis of naturally occurring and radiation-induced breakpoint locations in human chromosomes 1, 2 and 4.

The locations of observed breaks in three pairs of painted chromosomes from radiation-exposed and unexposed human peripheral blood lymphocytes are described. No difference in the observed breakpoint locations was seen from people exposed at Chernobyl, from healthy controls or from blood exposed to 2 Gy 137Cs in vitro. However, the distribution of observed breaks within the painted chromosomes was not random. Fewer breaks and rearrangements were observed near the ends of the chromosome arms. Three explanations for these findings were considered: cell selection, non-random efficiency of detection and non-random breakage or repair. Cell selection does not appear to be plausible because the distribution of observed breaks induced in vitro is not different from those induced in vivo. Non-random efficiency of detection is not supported by the data. Non-random breakage or repair appears to be the most likely explanation, although the mechanism(s) by which this occurs is unknown.

An improved method to determine cell viability by simultaneous staining with fluorescein diacetate-propidium iodide.

A rapid, simultaneous double-staining procedure using fluorescein diacetate (FDA) and propidium iodide (PI) is described for use in the determination of cell viability in cell suspension. Air-dried slide preparations can be made from the cell suspensions so that an accurate estimate of the viability of the cells in the original suspension can be made up to 1 week later. Viable cells fluoresce bright green, while nonviable cells are bright red. Furthermore, when FDA-PI staining is compared to trypan blue dye exclusion as a method to determine cell viability, FDA-PI is found to be more consistent over prolonged periods of exposure to the dyes. Therefore, double staining with FDA-PI is a rapid, convenient, and reliable method to determine cell viability.

Response of delayed (K+) channels to the time-dependent clamping functions in squid giant axon. II. Descending ramps, hyperbolae, and exponentials.

Squid giant axons are voltage-clamped with decaying ramp, hyperbolic, and exponential potential functions to determine an input potential function that generates parametric current density vs. membrane potential (I-V) plots best approximating the I-V curves generated from the steady state delayed (K+) current densities at a series of step clamp potentials. The optimum potential function must produce consistent I-V plots over an extended range of decay periods. A five-millisecond step clamp at the largest depolarizing potential in the experiment insures identical initial conditions for all potential functions. Although all parametric I-V curves are sensitive to K+ accumulation in the periaxonal space, the alteration of the I-V curves due to this accumulation is minimized for the hyperbolic and exponential decay functions. The advantages of these functions for the rapid generation of I-V curves are discussed.

Response of delayed (K+) channels to the time-dependent clamping function in squid giant axon. I. Ascending ramps.

Squid giant axons are voltage-clamped with ascending potential ramps whose slopes range from 0.5 mV/msec to 60 mV/msec and delayed (K+) currents are observed. The parametric current-voltage curves exhibit a delay period of minimal current followed by a rapid increase of current toward a final steady state. Both the initial delay and the slope of the subsequent rising phase increase with increasing ramp slope. When the Hodgkin-Huxley equations are used to generate theoretical current-voltage curves, the sharp difference between the delay and rising phases is muted and the ramp slope must be increased to produce an adequate representation of the data. A muted biphasic response is also observed when the current-voltage curves are generated using modified Hodgkin-Huxley parameters and a correction for K+ accumulation in the periaxonal space. These modified equations provide an accurate fit for step-potential clamp current data. Since the ramp experiments include all relevant clamping potentials, the experiments provide a sensitive test for kinetic models of K+ on flow in the delayed (K+) channels of squid giant axon.

Effects of some inhibitors on the temperature-dependent component of resting potential in lobster axon.

The resting membrane potential of the lobster axon becomes 5-8 mv more negative when the temperature of the perfusion solution is increased 10 degrees C. This potential change is about twice that predicted if the axon membrane potential followed that expected for a potassium ion electrode potential. When the inhibitors, 2, 4-dinitrophenol, sodium cyanide, and sodium azide, were added separately to the perfusion medium the potential change was reduced to about 1.4 times that predicted for a potassium ion electrode potential. Assays of axons exposed to these inhibitors showed that ATP levels were reduced to about one-fourth that obtained for control axons. Ouabain added to the perfusion medium reduced the potential change to that expected for a potassium ion electrode potential. These results suggest that the resting potential changes with temperature as a result of the activity of an electrogenic ion pump.

Voltage clamp studies on the effect of internal cesium ion on sodium and potassium currents in the squid giant axon.

Isolated and cleaned giant axons of Loligo pealii were internally perfused with solutions containing cesium sulfate and potassium fluoride. Membrane currents obtained as a function of clamped membrane potentials indicated a severe depression of the delayed outward current component normally attributed to potassium ion movement. Steady-state currents showed a negative slope in the potential range from -45 to -5 mv which corresponded to the negative slope for the peak sodium current relation vs. membrane potential which suggested long duration sodium currents. Using sodium-free sea water externally, sodium currents were separated from total currents and these persisted for longer times than normal. This result suggested that internal cesium ion delays the sodium conductance turnoff. The separated nonsodium currents showed an abnormal rectification as compared with those predicted by the independence principle, such that while potassium permeability appeared normal at the resting potential, its value decreased progressively with increasing depolarization.

Internally perfused axons: effects of two different anions on ionic conductance.

Voltage-clamizped giant axons of squid, internally perfused with potassiumt chloride solutions, showed reduced initial transient memnbrane conductance to voltage and increased overall (leakage) conductance. Unclamtped axons showed reduced action and resting potentials. Ionic conductances and memtbrane potentials were maintained or restored by perfusion with potassiuwn fluoride solutions. As much as 90 percent of internal fluoride could be replaced with chloride without alterationt of normal properties of membrane.