Percutaneous Radiofrequency Ablation of Pulmonary Metastases from Colorectal Carcinoma: Prognostic Determinants for Survival

Background Preliminary results have shown that percutaneous radiofrequency ablation (RFA) may play a useful role in patients with inoperable lung tumors. This series evaluated the prognostic features for survival in nonsurgical candidates who underwent percutaneous RFA of pulmonary metastases from colorectal carcinoma.Methods Fifty-five patients not suitable for surgery underwent percutaneous RFA for colorectal pulmonary metastases. All clinical and treatment-related data were collected prospectively. The primary end point of the study was overall survival, defined from the time of RFA intervention. Univariate and multivariate analyses were performed to identify statistically significant prognostic parameters for overall survival.Results The overall median survival was 33 months (range, 4–40 months), with actuarial 1-, 2-, and 3-year survival of 85%, 64%, and 46%, respectively. Univariate analysis demonstrated that largest size of lung metastasis (P < .001), location of lung metastases (P = .032), and repeat percutaneous RFA for pulmonary recurrence (P = .024) were statistically significant for overall survival. Multivariate analysis demonstrated that largest size of lung metastasis >3 cm was independently associated with a reduced overall survival (P = .003).Conclusions Percutaneous lung RFA may play a useful role in nonsurgical candidates with colorectal pulmonary metastases. However, the survival benefit of this interventional procedure for patients with a pulmonary metastasis >3 cm was limited.     

The faster the better: anastomosis time influences patient survival after deceased donor kidney transplantation

Despite a continuously growing knowledge of the impact of factors on kidney graft function, such as donor age, body mass index, and cold ischemia time, few data are available regarding anastomosis time (AT) and its impact on long‐term results. We investigated whether surgical AT correlates with patient and graft survival after kidney transplantation performing a retrospective analysis of 1245 consecutive deceased donor kidney transplantations between 01/2000 and 12/2010 at Innsbruck Medical University. Kaplan–Meier and log‐rank analyses were carried out for 1‐ and 5‐year patient and graft survival. AT was defined as time from anastomosis start until reperfusion. Median AT was 30 min. Five‐year survival of allografts with an AT >30 min was 76.6% compared with 80.6% in the group with AT <30 min (P = 0.027). Patient survival in the group with higher AT similarly was inferior with 85.7% after 5 years compared with 89.6% (P < 0.0001) [Correction added on February 18, 2015, after first online publication: the percentage value for patient survival was previously incorrect and have now been changed to 89.6%]. Cox regression analysis revealed AT as an independent significant factor for patient survival (HR 1.021 per minute; 95% CI 1.006–1.037; P = 0.006). As longer AT closely correlates with inferior long‐term patient survival, it has to be considered as a major risk factor for inferior long‐term results after deceased donor kidney transplantation.     

Methylene blue-assisted lymph node dissection in combination with ex vivo sentinel lymph node mapping in gastric cancer

Aims:  Lymph node (LN) stage is still the strongest prognostic marker in potentially curable gastric cancer. Accuracy of histopathological lymph node assessment depends on the number of investigated LNs and detection rate of metastases and micrometastases. The aim was to perform a feasibility study employing intra-arterial methylene blue injection – a novel method to improve LN harvest – and ex vivo sentinel LN mapping.
Methods and results:  A total of 33 cases were enrolled, including 14 retrospective cases that served as a control group. The methylene group showed a highly significant improved mean LN harvest compared with unstained cases, with 38 ± 14 versus 21 ± 10 LNs ( P  < 0.001), respectively. The detection rate of ex vivo sentinel mapping was 88%. No skip metastases occurred.
Conclusion:  Both techniques have the potential to improve the accuracy of histopathological LN staging and can be combined successfully.     

Tolerability of N-chlorotaurine plus ammonium chloride in the rabbit and human eye - a phase 1 clinical study

Background  N-chlorotaurine (NCT), an endogenous mild antiseptic, is well-tolerated by application to the human conjunctiva and has been shown to offer beneficial effects in infectious conjunctivitis. Animal tests revealed improved efficacy of a combination of NCT with ammonium chloride in adenoviral conjunctivitis. The aim of this study was to evaluate the tolerability of NCT plus ammonium chloride in the healthy rabbit and human eye. Methods  First, a tolerability study was performed in rabbits. In a blinded and randomized fashion, one eye was treated with the test medication, the other one with 0.9% saline. Twenty-one animals (three per concentration) were treated with one drop every 2 hours for 6 days. Second, in two volunteers one drop of a defined concentration was applied to one eye every 15 min for 1 hour, saline to the control eye. Four different concentrations were tested on different days. Third, a double-blind, randomized phase 1 study in 13 healthy volunteers was performed. One drop of 0.1% NCT plus 0.1% NH₄Cl versus saline was applied every 15 min within the first hour, followed by four drops every 2 hours. This regimen was done daily for 5 days. Results  In rabbits, no side effects were seen with 0.1% NCT plus 0.1% NH₄Cl, while higher concentrations sometimes caused short-time and minimal conjunctival injection and secretion after dosing. By 1% NCT plus 1% NH₄Cl, these effects were moderate, but disappeared again without any detectable residues. In the pilot study with two volunteers, treatment with 0.5% NCT plus 0.1% NH₄Cl caused medium-scale eye burning for 30 seconds, while 0.1% NCT plus 0.1% NH₄Cl was very well-tolerated, with no or minimal burning for a few seconds. In the subsequent phase 1 study, 0.1% NCT plus 0.1% NH₄Cl was well-tolerated by all subjects except for minimal eye burning for a few seconds after dropping. No objective signs of eye changes could be detected in the human beings. Conclusion  The results of this study clearly demonstrate the good tolerability of a promising NCT formulation with improved activity.     

NO- and haem-independent activation of soluble guanylyl cyclase: molecular basis and cardiovascular implications of a new pharmacological principle

1. Soluble guanylyl cyclase (sGC) is the only proven receptor for the ubiquitous biological messenger nitric oxide (NO) and is intimately involved in many signal transduction pathways, most notably in regulating vascular tone and platelet function. sGC is a heterodimeric (alpha/ss) protein that converts GTP to cyclic GMP; NO binds to its prosthetic haem group. Here, we report the discovery of a novel sGC activating compound, its interaction with a previously unrecognized regulatory site and its therapeutic implications. 2. Through a high-throughput screen we identified BAY 58-2667, an amino dicarboxylic acid which potently activates sGC in an NO-independent manner. In contrast to NO, YC-1 and BAY 41-2272, the sGC stimulators described recently, BAY 58-2667 activates the enzyme even after it has been oxidized by the sGC inhibitor ODQ or rendered haem deficient. 3. Binding studies with radiolabelled BAY 58-2667 show a high affinity site on the enzyme. 4. Using photoaffinity labelling studies we identified the amino acids 371 (alpha-subunit) and 231 - 310 (ss-subunit) as target regions for BAY 58-2667. 5. sGC activation by BAY 58-2667 results in an antiplatelet activity both in vitro and in vivo and a potent vasorelaxation which is not influenced by nitrate tolerance. 6. BAY 58-2667 shows a potent antihypertensive effect in conscious spontaneously hypertensive rats. In anaesthetized dogs the hemodynamic effects of BAY 58-2667 and GTN are very similar on the arterial and venous system. 7. This novel type of sGC activator is a valuable research tool and may offer a new approach for treating cardiovascular diseases.     

Voiding cystourethrography using the suprapubic versus transurethral route in infants and children: results of a prospective pain scale oriented study

PURPOSE: We determined the advantages and disadvantages of different types of contrast medium injection into the bladder for imaging children during evaluation for urinary tract infection in regard to child behavior and distress during urethral catheterization or suprapubic puncture. MATERIALS AND METHODS: From December 2000 to September 2001 we prospectively compared transurethral catheter and suprapubic voiding cystourethrography in children with a history of urinary tract infection. A total of 65 children with a mean age of 33.8 months were entered into the study, of whom 32 underwent transurethral catheterization and 33 underwent suprapubic puncture with topical anesthesia. Each child was evaluated, particularly in regard to discomfort and pain using an objective pain score that measures stress and pain during a medical procedure. RESULTS: Objective pain score recording showed a mean pain score plus or minus SD of 4.25 +/- 1.3 in the transurethral catheterization and 3.03 +/- 1.21 in the suprapubic puncture groups. Correlation studies of age in the 2 groups also showed a significant impact of age on the objective pain score. In the transurethral group the score increased with age (p <0.001), whereas in the suprapubic group it decreased with age (p <0.001). CONCLUSIONS: The current study shows that the suprapubic puncture technique with topical anesthesia was well tolerated and associated with a low pain score independent of patient age. Transurethral catheterization was also tolerated but it was associated with a low pain score only in the younger age group. Thus, we recommend that voiding cystourethrography in children older than 24 months should be done via the suprapubic route.