Lymphangiosis carcinomatosa in squamous cell carcinomas of larynx and hypopharynx – value of conventional evaluation and additional immunohistochemical staining of D2-40

<p>Abstract</p> <p>Background</p> <p>Recent studies revealed a predictive value of lymphatic vessel invasion (L1) for the nodal metastasizing and poor prognosis in malignant tumors at different sites. The monoclonal antibody D2-40 (podoplanin) stains specifically endothelial cells of lymphatic vessels and improves the search for L1. However, the importance of this immunohistochemical staining was not investigated in squamous cell carcinomas (SCC) of larynx and hypopharynx.</p> <p>Aim</p> <p>This study was performed to compare the diagnostic potential of convential and immunohistochemical determination of L1 in SCC of larynx and hypopharynx with special respect to the predictive value for nodal metastasizing and prognosis.</p> <p>Methods</p> <p>119 SCCs of the larynx (n = 70) respectively hypopharynx (n = 49) were investigated. The lymphatic vessel invasion was assessed by conventional method (HE stain) and immunohistochemical staining with an antibody against D2-40 (DAKO, Germany). Immunohistochemistry was performed in accordance with manufacturer's protocol. L1 was searched microscopically in a standardized magnification (×200) in serial sections of tumor samples (1 section per cm tumor diameter).</p> <p>Results</p> <p>The immunohistochemical investigation did not show significant advantages for the prediction of regional nodal metastases. Despite a low sensitivity (< 50%) in both methods, the specifity can reach 80%. The negative predictive value in both methods seems acceptable (up to 80%), whereas the positive predictive value is not higher than 64%. Cases with L1 detected either conventionally or immunohistochemically did not show a significant shorter survival than cases with L0. However, a non-significant shorter survival was found. Only in SCC of hypopharynx, a combination of both methods revealed patients with a significant worse prognosis.</p> <p>Conclusion</p> <p>The status of lymphatic vessel invasion should be documented in standardized tumor reports. A benefit of an additional immunohistochemical investigation was not found, for the daily routine HE-stain seems sufficient.</p

Seton drainage prior to transanal advancement flap repair: useful or not?

Introduction: Transanal advancement flap repair (TAFR) provides a useful tool in the treatment of high transsphincteric fistulas. Recent studies indicate that TAFR fails in one out of three patients. Until now, no definite predictive factor for failure has been identified. Although some authors have reported that preoperative seton drainage might improve the outcome of TAFR, this could not be confirmed by others. We conducted the present study to assess the influence of preoperative seton drainage on the outcome of TAFR in a relatively large series. Methods: Between December 1992 and June 2008, a consecutive series of 278 patients [M/F = 179:99, median age 46 years (range, 19-73 years)] with cryptoglandular, transsphincteric fistula, passing through the upper or middle third of the external anal sphincter underwent TAFR. Patients were recruited from the colorectal units of two university hospitals (Erasmus Medical Center, Rotterdam, n = 211; and Leiden University Medical Center, Leiden, n = 67). Baseline characteristics did not differ between the two clinics. Sixty-eight of these patients underwent preoperative seton drainage for at least 2 months and until the day of the flap repair. Results: Median healing time was 2.2 months. In patients without preoperative seton drainage, the healing rate was 63%, whereas the healing rate was 67% in patients who underwent preoperative seton drainage. This difference was not statistically significant. No differences in healing rates were found between the series from Leiden and Rotterdam. Conclusion: Preoperative seton drainage does not improve the outcome of TAFR

Identification of epithelialization in high transsphincteric fistulas

textabstractBackground At present, transanal advancement flap repair (TAFR) is the treatment of choice for transsphincteric fistulas passing through the upper and middle third of the external anal sphincter. It has been suggested that epithelialization of the fistula tract contributes to the failure of the treatment. The aim of this study was to assess the prevalence of epithelialization of the fistula tract and to study its effect on the outcome of TAFR and TAFR combined with ligation of the intersphincteric fistula tract (LIFT). Methods Forty-four patients with a high transsphincteric fistula of cryptoglandular origin underwent TAFR. Nine of these patients underwent a combined procedure of TAFR with LIFT. In all patients the fistula tract was excised from the external opening up to the outer border of the external anal sphincter. In patients undergoing TAFR combined with LIFT an additional central part of the intersphincteric fistula tract was excised. A total of 53 specimens were submitted. Histopathological examination of the specimens was carried out by a pathologist, blinded for clinical data. Results Epithelialization of the distal and intersphincteric fistula tract was observed in only 25 and 22% of fistulas, respectively. There was no difference in outcome between fistulas with or without epithelialization. Conclusions Epithelialization of high transsphincteric fistulas is rare and does not affect the outcome of TAFR and TAFR combined with LIFT

Delayed intracardial shunting and hypoxemia after massive pulmonary embolism in a patient with a biventricular assist device

We describe the interdisciplinary management of a 34-year-old woman with dilated cardiomyopathy three months postpartum on a cardiac biventricular assist device (BVAD) as bridge to heart transplantation with delayed onset of intracardial shunting and subsequent hypoxemia due to massive pulmonary embolism. After emergency surgical embolectomy pulmonary function was highly compromised (PaO2/FiO2 54) requiring bifemoral veno-venous extracorporeal membrane oxygenation. Transesophageal echocardiography detected atrial level hypoxemic right-to-left shunting through a patent foramen ovale (PFO). Percutaneous closure of the PFO was achieved with a PFO occluder device. After placing the PFO occluder device oxygenation increased significantly (Δ paO2 119 Torr). The patient received heart transplantation 20 weeks after BVAD implantation and was discharged from ICU 3 weeks after transplantation

Characteristic Evolution and Matching

I review the development of numerical evolution codes for general relativity based upon the characteristic initial value problem. Progress in characteristic evolution is traced from the early stage of 1D feasibility studies to 2D axisymmetric codes that accurately simulate the oscillations and gravitational collapse of relativistic stars and to current 3D codes that provide pieces of a binary black hole spacetime. Cauchy codes have now been successful at simulating all aspects of the binary black hole problem inside an artificially constructed outer boundary. A prime application of characteristic evolution is to extend such simulations to null infinity where the waveform from the binary inspiral and merger can be unambiguously computed. This has now been accomplished by Cauchy-characteristic extraction, where data for the characteristic evolution is supplied by Cauchy data on an extraction worldtube inside the artificial outer boundary. The ultimate application of characteristic evolution is to eliminate the role of this outer boundary by constructing a global solution via Cauchy-characteristic matching. Progress in this direction is discussed.Comment: New version to appear in Living Reviews 2012. arXiv admin note: updated version of arXiv:gr-qc/050809

Laboratory toxicity studies demonstrate no adverse effects of Cry1Ab and Cry3Bb1 to larvae of Adalia bipunctata (Coleoptera: Coccinellidae): the importance of study design

Scientific studies are frequently used to support policy decisions related to transgenic crops. Schmidt et al., Arch Environ Contam Toxicol 56:221–228 (2009) recently reported that Cry1Ab and Cry3Bb were toxic to larvae of Adalia bipunctata in direct feeding studies. This study was quoted, among others, to justify the ban of Bt maize (MON 810) in Germany. The study has subsequently been criticized because of methodological shortcomings that make it questionable whether the observed effects were due to direct toxicity of the two Cry proteins. We therefore conducted tritrophic studies assessing whether an effect of the two proteins on A. bipunctata could be detected under more realistic routes of exposure. Spider mites that had fed on Bt maize (events MON810 and MON88017) were used as carriers to expose young A. bipunctata larvae to high doses of biologically active Cry1Ab and Cry3Bb1. Ingestion of the two Cry proteins by A. bipunctata did not affect larval mortality, weight, or development time. These results were confirmed in a subsequent experiment in which A. bipunctata were directly fed with a sucrose solution containing dissolved purified proteins at concentrations approximately 10 times higher than measured in Bt maize-fed spider mites. Hence, our study does not provide any evidence that larvae of A. bipunctata are sensitive to Cry1Ab and Cry3Bb1 or that Bt maize expressing these proteins would adversely affect this predator. The results suggest that the apparent harmful effects of Cry1Ab and Cry3Bb1 reported by Schmidt et al., Arch Environ Contam Toxicol 56:221–228 (2009) were artifacts of poor study design and procedures. It is thus important that decision-makers evaluate the quality of individual scientific studies and do not view all as equally rigorous and relevant

Fibrin glue and transanal rectal advancement flap for high transsphincteric perianal fistulas; is there any advantage?

BACKGROUNDS AND AIM: In recent decades, fibrin glue has appeared as an alternative treatment for high perianal fistulas. Early results seemed promising, with high success rates being reported. However, with increasing follow-up, the enthusiasm was tempered because of disappointing results. The aim of this retrospective study was to assess the additional value of fibrin glue in combination with transanal advancement flap, compared to advancement flap alone, for the treatment of high transsphincteric fistulas of cryptoglandular origin. MATERIALS AND METHODS: Between January 1995 and January 2006, 127 patients were operated for high perianal fistulas with an advancement flap. After exclusion of patients with inflammatory bowel disease or HIV, 80 patients remained. A consecutive series of 26 patients had an advancement flap combined with obliteration of the fistula tract with fibrin glue. Patients were matched for prior fistula surgery, and the advancement was performed identically in all patients. In the fibrin glue group, glue was installed retrogradely in the fistula tract after the advancement was completed and the fistula tract had been curetted. RESULTS: Minimal follow-up after surgery was 13 months [median of 67 months (range, 13-127)]. The overall recurrence rate was 26% (n=21). Recurrence rates for advancement flap alone vs the combination with glue were 13% vs 56% (p=0.014) in the group without previous fistula surgery and 23% vs 41% (p=0.216) in the group with previous fistula surgery. CONCLUSION: Obliterating the fistula tract with fibrin glue was associated with worse outcome after rectal advancement flap for high perianal fistula

Consumption of Bt Maize Pollen Expressing Cry1Ab or Cry3Bb1 Does Not Harm Adult Green Lacewings, Chrysoperla carnea (Neuroptera: Chrysopidae)

Adults of the common green lacewing, Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae), are prevalent pollen-consumers in maize fields. They are therefore exposed to insecticidal proteins expressed in the pollen of insect-resistant, genetically engineered maize varieties expressing Cry proteins derived from Bacillus thuringiensis (Bt). Laboratory experiments were conducted to evaluate the impact of Cry3Bb1 or Cry1Ab-expressing transgenic maize (MON 88017, Event Bt176) pollen on fitness parameters of adult C. carnea. Adults were fed pollen from Bt maize varieties or their corresponding near isolines together with sucrose solution for 28 days. Survival, pre-oviposition period, fecundity, fertility and dry weight were not different between Bt or non-Bt maize pollen treatments. In order to ensure that adults of C. carnea are not sensitive to the tested toxins independent from the plant background and to add certainty to the hazard assessment, adult C. carnea were fed with artificial diet containing purified Cry3Bb1 or Cry1Ab at about a 10 times higher concentration than in maize pollen. Artificial diet containing Galanthus nivalis agglutinin (GNA) was included as a positive control. No differences were found in any life-table parameter between Cry protein containing diet treatments and control diet. However, the pre-oviposition period, daily and total fecundity and dry weight of C. carnea were significantly negatively affected by GNA-feeding. In both feeding assays, the stability and bioactivity of Cry proteins in the food sources as well as the uptake by C. carnea was confirmed. These results show that adults of C. carnea are not affected by Bt maize pollen and are not sensitive to Cry1Ab and Cry3Bb1 at concentrations exceeding the levels in pollen. Consequently, Bt maize pollen consumption will pose a negligible risk to adult C. carnea

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD