Evaluation of current devices in single-incision laparoscopic colorectal surgery: a preliminary experience in 32 consecutive cases.

BACKGROUND: Single-incision laparoscopic colorectal surgery (SILS) suggests a promising alternative to conventional laparoscopic surgery. In this report we describe our initial experience with SILS for both right hemicolectomies and anterior resections. METHODS: Between June 2009 and May 2010, SILS was performed for 32 consecutive cases with benign and malignant pathology. Demographic data, intraoperative parameters, postoperative data, and pathologic data were assessed. RESULTS: Twenty-one SILS right hemicolectomies, ten ARs, and one abdominal perineal resection (APR) were performed. For SILS right hemicolectomies, one case required full "conversion" to a laparoscopic procedure. The median operating time was 85 min (range 45-150 min) and the median wound length was 5.0 cm (range 3.0-10.0 cm). Median number of lymph nodes extracted in malignant cases was 17(range 10-30) and the overall median length of stay was 6 days (range 5-11). For left-sided lesions, ten cases of ARs (7 high ARs, 2 low ARs, 1 ultralow AR) and one APR were performed. Three cases were completed successfully via the SILS procedure, four cases required one additional port, and four cases required full "conversion" to a laparoscopic procedure. The median operating time was 120 min (range 65-235 min) and the median wound length was 5.0 cm (range 3.0-7.0 cm). Overall median length of stay was also 6 days (range 5-21). There was one case of anastomotic leak and one case of postoperative bleeding. CONCLUSION: In our experience, SILS for right hemicolectomies is safe and effective with reproducible oncologic results. SILS AR, however, requires greater modifications in current devices and techniques. SILS AR can be performed for both malignant and benign diseases but additional ports may be necessary for the safe completion of the procedure.

Use of the Impella microaxial blood pump for ablation of hemodynamically unstable ventricular tachycardia.

Ablation for ventricular tachycardia remains a challenge with suboptimal procedural success rates. One of the major causes of difficulty is precipitous hypotension when ventricular tachycardia is induced precluding even rapid mapping of the arrhythmia. We report the successful use of the Impella microcirculatory axial blood flow pump in 3 patients with hemodynamically unstable ventricular tachycardia that allowed successful completion of the procedure. In these 3 patients, there was no evidence of Impella-related valvular disturbance, iatrogenic ventricular arrhythmias, or interference with mapping and ablation catheter movement.

Treatment of oral leukoplakia with carbon dioxide and potassium-titanyl-phosphate lasers: a comparison.

PURPOSE: To determine whether the treatment of oral leukoplakia with potassium-titanyl-phosphate (KTP) lasers versus CO(2) lasers results in lower recurrence rates. MATERIALS AND METHODS: Retrospective data were collected from the records of 30 patients (mean age 75.6 years) with 35 primary oral leukoplakia who had their lesions ablated by KTP laser, and 45 patients (mean age 59.9 years) with 59 primary oral leukoplakia who had CO(2) laser treatment. The recurrence rates of lesions between these 2 groups was then compared. RESULTS: A statistically significant (P = .049) reduction in recurrence rates for those patients treated with KTP lasers versus CO(2) lasers was found. CONCLUSION: The use of KTP lasers for the treatment of oral leukoplakia may result in lower recurrence rates than when using CO(2) lasers.

Molecular basis of fibrin clot elasticity.

Blood clots must be stiff to stop hemorrhage yet elastic to buffer blood's shear forces. Upsetting this balance results in clot rupture and life-threatening thromboembolism. Fibrin, the main component of a blood clot, is formed from molecules of fibrinogen activated by thrombin. Although it is well known that fibrin possesses considerable elasticity, the molecular basis of this elasticity is unknown. Here, we use atomic force microscopy (AFM) and steered molecular dynamics (SMD) to probe the mechanical properties of single fibrinogen molecules and fibrin protofibrils, showing that the mechanical unfolding of their coiled-coil alpha helices is characterized by a distinctive intermediate force plateau in the systems' force-extension curve. We relate this plateau force to a stepwise unfolding of fibrinogen's coiled alpha helices and of its central domain. AFM data show that varying pH and calcium ion concentrations alters the mechanical resilience of fibrinogen. This study provides direct evidence for the coiled alpha helices of fibrinogen to bring about fibrin elasticity.

Concurrent application of charge using a novel circuit prevents heat-related coagulum formation during radiofrequency ablation.

INTRODUCTION: Thromboembolism resulting from coagulum formation on the catheter and electrode surfaces is a serious complication with radiofrequency ablation procedures for heart rhythm disorders. Why coagulum occurs despite therapeutic heparinization is unclear. In this report, we demonstrate a novel approach to minimize coagulum formation based on the electromolecular characteristics of fibrinogen. METHODS AND RESULTS: Atomic force microscopy was used to establish that fibrinogen deposited on surfaces underwent conformational changes that resulted in spontaneous clot formation. We then immersed ablation catheters that were uncharged, negatively, or positively charged in heparinized blood for 30 minutes and noted the extent of clot formation. In separate experiments, ablation catheters were sutured to the ventricle of an excised porcine heart immersed in whole, heparinized blood and radiofrequency ablation performed for 5 minutes with and without charge delivered to the catheter tips. Electron microscopy of the catheter tips showed surface coverage of fibrin clot of the catheter to be 33.8% for negatively charged catheters, compared with 84.7% (P = 0.01) in noncharged catheters. There was no significant difference in surface coverage of fibrin clot between positively charged catheters (93.8%) and noncharged catheters (84.7%, P = ns). In contrast, the thickness of surface clot coverage for positively charged catheters was 87.5%, compared with 28.45% (P= 0.03) for noncharged catheters and 11.25% (P = 0.03) for negatively charged catheters, compared with noncharged catheters. CONCLUSIONS: We describe a novel method of placing negative charge on electrodes during ablation that reduced coagulum formation. This may decrease thromboembolism-related complications with radiofrequency ablation procedures.

Effect of Charge Delivery on Thromboembolism During Radiofrequency Ablation in Canines.

OBJECTIVES: This study investigated whether delivering negative charge to catheter tips reduces thromboembolism during catheter ablation. BACKGROUND: Radiofrequency (RF) ablation prevents atrial fibrillation that can cause stroke or death. However, ablation itself can cause stroke (2%) or silent ischemia (2% to 41%), possibly via particulate debris that embolizes after coagulum adherence to catheter surfaces. Coagulum formation on RF catheters can be prevented by applying negative charge, but it is unknown if charge reduces peripheral thromboembolism. METHODS: Paired (Charge ON vs. OFF) endocardial RF ablations were performed in 9 canines using nonirrigated RF catheters. Continuous negative charge was delivered via -100 µA of DC current applied to ablation catheter electrodes. Intracardiac echocardiography was used to navigate the catheter and to monitor coagulum formation. In a subset of 5 canines, microemboli flowing through polyester tubing between the femoral artery and vein (extracorporeal loop) were monitored with bubble counters and inline filter fabric. After each ablation, catheter-tip coagulum and blood particles deposited on the filters were quantified using photography and imaging software (ImageJ, U.S. National Institutes of Health, Bethesda, Maryland). RESULTS: Negative charge significantly decreased the extracorporeal loop median filter area covered by particles (n = 19 pairs) by 10.2 mm2 (p = 0.03), and decreased median filter particles by 349 (p = 0.03). Negative charge also decreased the percentage of the catheter tip surface area covered by coagulum (n = 39 pairs) by 7.2% (p = 0.03). CONCLUSIONS: Negative charge delivery to ablation catheter tips during RF ablation can reduce particulate embolization material in an extracorporeal loop, and potentially reduce thromboembolic risk associated with RF ablation.

Prevention of Coagulum Formation With Simultaneous Charge Delivery in Radiofrequency Ablation: A Canine Model.

OBJECTIVES: This study reports on a novel method to prevent coagulum formation by continuously delivering a negative charge to the catheter tip to repel negatively charged fibrinogen molecules during RF ablation. BACKGROUND: Radiofrequency (RF) ablation for cardiac arrhythmias is associated with a 70% incidence of coagulum formation on the catheter tip during ablation and a 10% incidence of thromboembolic events. Catheter tip thrombus can impede RF energy to the tissue, reducing efficacy and increasing procedure times. METHODS: A novel circuit was built to deliver a negative, fixed-offset, direct current-based charge using a 9-V battery, placed in parallel with an RF delivery unit during RF ablation. In in vivo canine experiments, standard ablation catheters were advanced into atria and ventricles under fluoroscopic guidance. The presence of thrombus with and without RF delivery was identified with intracardiac echocardiography. RESULTS: Scanning electron microscopy of the catheter tips showed clot coverage of the catheter tip to be 90% for noncharged catheters compared to 0% (p < 0.01) in negatively charged catheters. Volume of clot formed on the catheter tip decreased with increased amount of charge (140 ± 5.3 arbitrary units with no charge vs. 0 arbitrary units with a 100-µA current delivering negative charge, p < 0.01). Application of a negative charge did not affect the quality of the intracardiac electrogram or induce malignant ventricular arrhythmias. CONCLUSIONS: Negative-charge delivery to ablation catheter tips and tissue during RF ablation is feasible and safe and can eliminate coagulum formation, potentially reducing thromboembolic complications.

CSF otorrhea complicating temporal bone osteoradionecrosis in a patient with nasopharyngeal carcinoma.

A 44-year-old Chinese man with a history of nasopharyngeal carcinoma that was treated with radiotherapy presented with fluid in the middle ear. We performed a myringotomy and subsequently made a diagnosis of cerebrospinal fluid (CSF) leakage secondary to osteoradionecrosis of the temporal bone. To the best of our knowledge, this is only the second reported case of an otogenic CSF leak resulting from osteoradionecrosis of the temporal bone. This case highlights the controversial role of myringotomy in the management of CSF otorrhea.

Interaction of asymmetric ABCC9-encoded nucleotide binding domains determines KATP channel SUR2A catalytic activity.

Nucleotide binding domains (NBDs) secure ATP-binding cassette (ABC) transporter function. Distinct from traditional ABC transporters, ABCC9-encoded sulfonylurea receptors (SUR2A) form, with Kir6.2 potassium channels, ATP-sensitive K+ (K ATP) channel complexes. SUR2A contains ATPase activity harbored within NBD2 and, to a lesser degree, NBD1, with catalytically driven conformations exerting determinate linkage on the Kir6.2 channel pore. While homodomain interactions typify NBDs of conventional ABC transporters, heterodomain NBD interactions and their functional consequence have not been resolved for the atypical SUR2A protein. Here, nanoscale protein topography mapped assembly of monodisperse purified recombinant SUR2A NBD1/NBD2 domains, precharacterized by dynamic light scattering. Heterodomain interaction produced conformational rearrangements inferred by secondary structural change in circular dichroism, and validated by atomic force and transmission electron microscopy. Physical engagement of NBD1 with NBD2 translated into enhanced intrinsic ATPase activity. Molecular modeling delineated a complemental asymmetry of NBD1/NBD2 ATP-binding sites. Mutation in the predicted catalytic base residue, D834E of NBD1, altered NBD1 ATPase activity disrupting potentiation of catalytic behavior in the NBD1/NBD2 interactome. Thus, NBD1/NBD2 assembly, resolved by a panel of proteomic approaches, provides a molecular substrate that determines the optimal catalytic activity in SUR2A, establishing a paradigm for the structure-function relationship within the K ATP channel complex.

Common variation in the C-terminal region of the fibrinogen beta-chain: effects on fibrin structure, fibrinolysis and clot rigidity.

Fibrinogen BbetaArg448Lys is a common polymorphism, positioned within the carboxyl terminus of the Bbeta-chain of the molecule. Studies suggest that it is associated with severity of coronary artery disease and development of stroke. The effects of the amino acid substitution on clot structure remains controversial, and the aim of this study was to investigate the effect(s) of this polymorphism on fibrin clot structure using recombinant techniques. Permeation, turbidity, and scanning electron microscopy showed that recombinant Lys448 fibrin had a significantly more compact structure, with thin fibers and small pores, compared with Arg448. Clot stiffness, measured by means of a novel method using magnetic tweezers, was significantly higher for the Lys448 compared with the Arg448 variant. Clots made from recombinant protein variants had similar lysis rates outside the plasma environment, but when added to fibrinogen-depleted plasma, the fibrinolysis rates for Lys448 were significantly slower compared with Arg448. This study demonstrates for the first time that clots made from recombinant BbetaLys448 fibrinogen are characterized by thin fibers and small pores, show increased stiffness, and appear more resistant to fibrinolysis. Fibrinogen BbetaArg448Lys is a primary example of common genetic variation with a significant phenotypic effect at the molecular level.

Genetic regulation of fibrin structure and function: complex gene-environment interactions may modulate vascular risk.

BACKGROUND: Polymorphisms in the fibrinogen and factor XIII genes are associated with atherothrombotic risk, but clinical studies have produced inconsistent results and laboratory studies have not explained these findings. We aimed to investigate interactions between polymorphisms in the factor XIII and fibrinogen genes, fibrinogen concentrations, and other cardiovascular risk factors in relation to fibrin structure and function. METHODS: We used permeation analysis and electron microscopy to investigate interactions between fibrin structure, factor XIII Val34Leu, fibrinogen Aalpha Thr312Ala, fibrinogen Bbeta Arg448Lys, and fibrinogen concentrations in plasma and purified systems. FINDINGS: Increased fibrinogen concentrations were associated with decreases in permeability, with tighter clot structures in the presence of factor XIII 34Val alleles compared with those in the presence of 34Leu alleles. Findings were confirmed by scanning electron microscopy of fibrin. Similar changes in permeability were noted for Aalpha fibrinogen 312Ala compared with that for 312Thr. INTERPRETATION: Our results show interactions between coding polymorphisms in fibrinogen and factor XIII and fibrinogen concentrations that modify fibrin and explain the apparent paradox between epidemiological studies of factor XIII 34Leu and reported in-vitro effects on fibrin structure and function. We suggest a potential complexity of gene-gene and gene-environment interactions in determining cardiovascular risk.