Jukka T. Salminen

Incipient Angiogenesis in Barrett’s Epithelium and Lymphangiogenesis in Barrett’s Adenocarcinoma

PURPOSEnBarretts esophagus (BE), a precancerous condition for Barretts adenocarcinoma, is classically characterized by flames of salmon-colored mucosa extending into normal pale esophageal mucosa. This flaming is thought to be a consequence of continuous erosis of mucosa caused by chronic reflux. Another characteristic feature of Barretts adenocarcinoma patients is the frequent development of lymph node metastases. We addressed whether onset of angiogenesis occurs in BE and if the lymphatic system might provide a route for Barretts adenocarcinoma cells to infiltrate regular lymph nodes.nnnPATIENTS AND METHODSnFifteen surgically resected Barretts dysplasia or adenocarcinoma patients were included. Immunohistochemistry and a modified whole mount analysis were used.nnnRESULTSnThe incipient angiogenesis originates from the pre-existing vascular network in the lamina propria and infiltrates Barretts epithelium, giving its ominous salmon-red color. Barretts epithelium-specific goblet cells express vascular endothelial growth factor (VEGF)-A. The immature blood vessels show a relative absence of smooth muscle actin (SMA)-positive mural cells and express VEGF receptor (VEGFR)-2 and matrix metalloproteinase (MMP)-9 on their exterior. Coexpression of VEGF-C and its receptor VEGFR-3 on lymphatic vessels is demonstrated.nnnCONCLUSIONnBE is strongly neovascularized not eroded. This novel concept of a molecular mechanism of the origin of BE might emphasize why precancerous BE can give rise to the more cancerous dysplasia and Barretts adenocarcinoma stages. In addition, adenocarcinoma cells induce lymphangiogenesis. The new lymphangiogenic vessels might provide a systemic route for adenocarcinoma cells to invade circulation and induce lymph node metastasis.

Tumor necrosis factor-?? in a porcine bronchial model of obliterative bronchiolitis1

Background. In posttransplant obliterative bronchiolitis (OB), the major pathologic features are inflammation, epithelial cell injury, fibrosis, and obliteration of the small airways. Tumor necrosis factor (TNF)-&agr; is a cytokine known to mediate and augment the inflammatory reaction and to enhance fibroblast proliferation. We assessed the role of TNF-&agr; in the development of OB in our heterotopic porcine bronchial transplantation model. Methods. Three groups were formed: autografts, nontreated allografts, and allografts treated with preoperative anti–TNF-&agr; monoclonal antibody (infliximab) infusion. The implants were harvested on days 2, 4, 7, 11, 14, 21, and 28 for histologic and immunohistochemical analysis. Results. TNF-&agr; inhibition reduced inflammation, rate of epithelial loss, fibrosis, and obliteration early in the development of OB. In the epithelium, the numbers of TNF-&agr;–positive epithelial and inflammatory cells and macrophages were significantly lower in treated than in nontreated allografts on day 4; furthermore, in the epithelium and in the bronchial wall, invasion of CD8+ lymphocytes was significantly decreased during the first week. Conclusions. These results indicate that TNF-&agr; promotes the development of OB, and inhibition of TNF-&agr; may prove beneficial in a clinical setting.

Excellent functional result in children after correction of anomalous origin of left coronary artery from the pulmonary artery – a population-based complete follow-up study☆

Surgical strategy to construct a two-coronary system for a patient with anomalous origin of left coronary artery from pulmonary artery (ALCAPA) has evolved with time. Limited long-term follow-up data are available on these children. We report population-based follow-up in children operated on for ALCAPA. In total, 29 patients underwent aortic reimplantation of ALCAPA between 1979 and 2006. Twenty (69%) children were repaired with direct aortic implantation, five (17%) with a modified tubular extension technique, and four (14%) patients with an intrapulmonary baffling technique. Early postoperative mortality (<30 days) was 17%. No late mortality (>30 days) was detected. The median length of follow-up was 11 years (range 10 months-27 years). Global left ventricular function by echocardiography (M-mode) was within normal limits (>30%) in all patients one year after operation. Functionally, 80% of patients were classified in NYHA class I, 20% in NYHA II, and 0% in NYHA classes III/IV at the time of the last examination. Excellent results with good long-term outcome can be achieved in infants with ALCAPA using reimplantation techniques. Normalization of cardiac function is expected within the first year in all operative survivors with a patent coronary system.

Prevention of postoperative pericardial adhesions in children with hypoplastic left heart syndrome

Reoperations for congenital cardiac defects are associated with an increased surgical risk due to adhesions. We compared the capability of a polytetrafluoroethylene (PTFE) membrane, synthetic polyethyleneglycol hydrogel (PEG), and a combination of them to prevent postoperative pericardial adhesions in patients with hypoplastic left heart syndrome (HLHS). Eighteen consecutive patients with HLHS were included. At the end of the Norwood I operation the cranial and the caudal half of the heart of each patient was randomized to receive a PTFE membrane, a synthetic PEG, a combination of them, or no treatment (control). Tenacity and density of adhesions, epicardial visibility, and adhesions between the heart and the sternum were analyzed semiquantitatively at a subsequent bidirectional Glenn operation. The PTFE membrane significantly decreased adhesion formation between the heart and the sternum (P<0.001). However, the PTFE membrane, with or without synthetic PEG, impaired epicardial visibility (P<0.05) when compared to synthetic PEG or controls. Synthetic PEG alone did not significantly reduce the formation of pericardial adhesions. Tenacity and density of adhesions were not affected by any of the treatment modalities. The PTFE membrane significantly decreases postoperative adhesions between the heart and the sternum, but impairs epicardial visibility. Synthetic PEG does not prevent formation of pericardial adhesions.

Prenatal Diagnosis Improves the Postnatal Cardiac Function in a Population-Based Cohort of Infants with Hypoplastic Left Heart Syndrome

BACKGROUNDnPrenatal diagnosis of hypoplastic left heart syndrome (HLHS) enables planning of perinatal care and is known to be associated with more stable preoperative hemodynamics. The impact on postnatal myocardial function is poorly known. The aim of this study was to determine the impact of prenatal diagnosis of HLHS on postnatal myocardial function.nnnMETHODSnA consecutively encountered cohort of 66 infants with HLHS born between 2003 and 2010 in Finland was retrospectively reviewed. Twenty-five infants had prenatal diagnoses. Postnatal global and segmental right ventricular fractional area change, strain rate, and myocardial velocity were analyzed from the apical four-chamber view using Velocity Vector Imaging. Preoperative hemodynamic status and end-organ damage measurements were the lowest arterial pH, highest lactate, alanine aminotransferase, and creatinine. Early mortality was studied until 30 days after Norwood procedure.nnnRESULTSnPrenatally diagnosed infants had better cardiac function (fractional area change, 27.9 ± 7.4% vs 21.1 ± 6.3%, P = .0004; strain rate, 1.1 ± 0.6/1.3 ± 1.0 vs 0.7 ± 0.2/0.7 ± 0.3 1/sec, P = .004/.003; myocardial velocity, 1.6 ± 0.6/2.0 ± 1.1 vs 1.3 ± 0.4/1.4 ± 0.4 cm/sec, P = .0035/.0009). Mechanical dyssynchrony was similar in both groups (P > .30). Infants diagnosed prenatally had less acidosis (pH = 7.30 vs 7.25, P = .005) and end-organ dysfunction (alanine aminotransferase, 33 ± 38 vs 139 ± 174 U/L, P = .0001; creatinine, 78 ± 18 vs 81 ± 44 mmol/L, P = .05). No deaths occurred among the prenatally diagnosed infants, but four deaths were recorded among postnatally diagnosed infants (P = .15).nnnCONCLUSIONSnA prenatal diagnosis of HLHS is associated with improved postnatal right ventricular function, reduced metabolic acidosis, and end-organ dysfunction.

Primary Pulmonary Vein Stenosis: Outcomes, Risk Factors, and Severity Score in a Multicentric Study

BACKGROUNDnPrimary pulmonary vein stenosis (PPVS) still carries a poor prognosis, and prognostic factors remain controversial. The aim of this study was to determine outcomes and prognostic factors after PPVS repair in the current era.nnnMETHODSnThirty patients with PPVS and a normal pulmonary vein (PV) connection operated on in 10 European/North American centers (2000-2012) were included retrospectively. A specific PVS severity score was developed based on the assessment of each PV. Studied end points were death, PV reoperation, and restenosis. A univariate and multivariate risk analysis was performed.nnnRESULTSnThe mean number of affected PVs per patient was 2.7 ± 1.1. Sutureless repair was used in 21 patients (70%), endovenectomy was used in 5 patients, and patch venoplasty was used in 4 patients. Overall PV restenosis, reoperation, and mortality occurred in 50%, 40%, and 30% of patients respectively. Freedom from mortality, reoperation, and restenosis at 8 years of follow-up was 70% ± 8%, 62% ± 8%, and 47% ± 9%, respectively. Restenosis and mortality rates after sutureless repair versus nonsutureless repair were 57% (nxa0= 12 of 21) versus 33% (nxa0= 3 of 9) (pxa0= 0.42) for restenosis and 38% (nxa0= 8 of 21) versus 11% (nxa0= 1 of 9) (pxa0= 0.21) for mortality. Patients selected for a sutureless technique were younger and smaller and had more severe disease before operation. A postoperative high PVS score and pulmonary hypertension 1 month after the operation were independent risk factors for restenosis (hazard ratio [HR], 1.34; pxa0= 0.002 and HR, 6.81; pxa0= 0.02, respectively), reoperation (HR, 1.24; pxa0= 0.01 and HR, 7.60; pxa0= 0.02), and mortality (HR, 1.39; pxa0= 0.01 and HR, 39.5; pxa0= 0.008).nnnCONCLUSIONSnPrimary PVS still has a guarded prognosis in the current era despite adoption of the sutureless technique. Postoperative pulmonary hypertension and severity of disease evaluated by a new severity score are independent prognostic factors regardless of surgical technique.

High‐dose methylprednisolone and endothelial glycocalyx in paediatric heart surgery

Corticosteroids are used in paediatric heart surgery to attenuate systemic inflammatory response. Glycocalyx regulates vascular permeability, shear stress and cell adhesion on the endothelium. Syndecan‐1 serves as a biomarker of glycocalyx degradation. Hydrocortisone decreased endothelial glycocalyx degradation in an experimental model. Our hypothesis was that high‐dose methylprednisolone decreases glycocalyx degradation as measured by plasma sydecan‐1 concentration in children undergoing cardiac surgery.

Subacute primary Candida lung abscess.

A case of primary subacute Candida lung abscess is described. The most reliable way to diagnose a rare pulmonary disease is to perform an open lung biopsy. A review of the literature suggests that the diagnosis of a primary subacute abscess due to Candida albicans in vivo is unique.

The effect of continuous wound infusion of ropivacaine on postoperative pain after median sternotomy and mediastinal drain in children

Postoperative pain after median sternotomy is usually treated with i.v. opioids. We hypothesized that continuous wound infusion of ropivacaine decreases postoperative morphine consumption and improves analgesia in children who undergo cardiac surgery.

High‐sequence diversity and structural conservation in the human T‐cell receptor β junctional region during thymic development

The T‐cell repertoire depends on intrathymic genetic rearrangement events in the T‐cell receptor (TCR) locus, followed by positive and negative selection. The repertoire thus generated is highly diverse, but recent data indicate that the recombination of gene segments is less stochastic than previously suggested. Very little is known of the junctional complementarity determining region 3 (CDR3), which is to a large degree not germline encoded. We have analyzed the development of the human TCR β CDR3 repertoire, from the nonselected CD4+CD8+CD3− cells up to the fully selected CD4+CD8− thymocytes. In addition to spectratyping, a fraction of the CDR3 repertoire was sequenced and a structural in silico analysis of the CDR3 loop characteristics performed. Our data show that the thymic TCR repertoire is extremely diverse, and the effect of the selection events can be detected as a measurable loss of polyclonality in the CDR3 loop. However, the main physicochemical features of the CDR3 loop were found already at the nonselected repertoire and showed no progressive changes during the selection. Thus, the main structural characteristics of the CDR3 loop were already determined by the recombination process and not significantly affected by the extensive thymocyte death associated with selection in the thymus.