Publications by authors named "Jukka T Salminen"

17 Publications

  • Page 1 of 1

Renal function and inflammatory response in neonates undergoing cardiac surgery with or without antegrade cerebral perfusion-a post hoc analysis.

Ann Card Anaesth 2021 Oct-Dec;24(4):434-440

Department of Anesthesia and Intensive Care, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Cardiopulmonary bypass (CPB) may lead to tissue hypoxia, inflammatory response, and risk for acute kidney injury (AKI). We evaluated the prevalence of AKI and inflammatory response in neonates undergoing heart surgery requiring CPB with or without antegrade cerebral perfusion (ACP).

Methods: Forty neonates were enrolled. The patients were divided into two groups depending on the use of ACP. AKI was classified based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Inflammatory response was measured using plasma concentrations of interleukins 6 (IL-6) and 10 (IL-10), white blood cell count (WBC), and C-reactive protein (CRP).

Results: Eight patients (20%) experienced AKI: five (29%) in the ACP group and three (13%) in the non-ACP group (P = 0.25). Postoperative peak plasma creatinine and urine neutrophil gelatinase-associated lipocalin were significantly higher in the ACP group than in the non-ACP group [46.0 (35.0-60.5) vs 37.5 (33.0-42.5), P = 0.044 and 118.0 (55.4-223.7) vs 29.8 (8.1-109.2), P = 0.02, respectively]. Four patients in the ACP group and one in the non-ACP group required peritoneal dialysis (P = 0.003). Postoperative plasma IL-6, IL-10, and CRP increased significantly in both groups. There were no significant differences between the ACP and non-ACP groups in any of the inflammatory parameters measured.

Conclusions: No significant difference in the AKI occurrence or inflammatory response related to CPB modality could be found. In our study population, inflammation was not the key factor leading to AKI. Due to the limited number of patients, these findings should be interpreted with caution.
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http://dx.doi.org/10.4103/aca.ACA_183_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617397PMC
November 2021

Development of Human Leukocyte Antigen (HLA) Antibodies Against Vascular Homograft Donor in Pediatric Heart Transplant Recipients.

Ann Transplant 2019 Aug 6;24:454-460. Epub 2019 Aug 6.

Department of Pediatric Nephrology and Transplantation, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

BACKGROUND The appearance of human leukocyte antigen (HLA) antibodies after solid organ transplantation predisposes recipients to graft dysfunction. In theory, vascular homografts, which are widely used in children with congenital heart defects, may cause allosensitization. MATERIAL AND METHODS In this single-center retrospective study, the presence of pre-existing HLA antibodies in pediatric heart transplant (HTx) recipients with a vascular homograft was evaluated in a cohort of 12 patients. HLA antibodies were screened before and after HTx and positive screening results were confirmed and identified using the Luminex® single antigen bead method. Endomyocardial biopsies (EMB) and coronary angiography studies were re-evaluated to assess the prevalence of acute rejections and coronary artery change in these patients. RESULTS At the time of HTx, 8 patients (67%) had HLA antibodies detected by the Luminex assay, none of which were heart donor specific (DSA). All patients had negative leukocyte crossmatch. One patient developed DSAs against homograft donor prior to HTx. After the HTx, 5 patients (42%) developed DSAs against the heart donor and 4 patients (40%) against the homograft donor. In 2 patients (17%), the antibodies were against both heart and homograft donors. The rejection rate or prevalence of coronary artery vasculopathy did not differ significantly between the homograft cohort and our historical controls. CONCLUSIONS Our results suggest that the prevalence of DSAs against homograft donor prior to HTx is relatively rare. However, almost half of the patients developed DSAs against homograft post-HTx. The clinical importance of these antibodies warrants further studies.
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http://dx.doi.org/10.12659/AOT.917232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698089PMC
August 2019

The effect of sildenafil on pleural and peritoneal effusions after the TCPC operation.

Acta Anaesthesiol Scand 2019 11 16;63(10):1384-1389. Epub 2019 Jul 16.

Department of Pediatric Cardiac Surgery, Children's Hospital, Helsinki University Hospital, Helsinki, Finland.

Background: We evaluated whether the administration of sildenafil in children undergoing the TCPC operation shortened the interval from the operation to the removal of the pleural and peritoneal drains.

Methods: We retrospectively reviewed the data of 122 patients who had undergone the TCPC operation between 2004 and 2014. Patients were divided into two groups on the basis of their treatments. Sildenafil was orally administered pre-operatively in the morning of the procedure or within 24 hours after the TCPC operation to the sildenafil group (n = 48), which was compared to a control group (n = 60). Fourteen patients were excluded from the study.

Results: The primary outcome measure was the time from the operation to the removal of the drains. The study groups had similar demographics. The median [interquartile range] time for the removal of drains (sildenafil group 11 [8-19] vs control group 11 [7-16] d, P = .532) was comparable between the groups. The median [interquartile range] fluid balance on the first post-operative day was significantly higher (P = .001) in the sildenafil group compared with controls (47 [12-103] vs 7 [-6-67] mL kg ). The first post-operative day fluid balance was a significant predictor for a prolonged need for drains in the multivariate analysis.

Conclusions: Sildenafil administration, pre-operatively or within 24 hours after the TCPC operation, did not reduce the required time for pleural and peritoneal drains but was associated with a significantly higher positive fluid balance.
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http://dx.doi.org/10.1111/aas.13431DOI Listing
November 2019

Procedural risk factors, incidence and timing of reintervention after treatment for native coarctation of the aorta in children: a population-based study†.

Eur J Cardiothorac Surg 2019 Mar;55(3):564-571

Department of Pediatric Cardiology, Children`s Hospital, University Hospital and University of Helsinki, Helsinki, Finland.

Objectives: The aim of the present study was to evaluate procedural risk factors, incidence and timing of reintervention because of recurrent aortic coarctation in children.

Methods: The study cohort consisted of 304 patients with isolated coarctation: 251 underwent surgery and 53 were treated percutaneously (40 balloon angioplasty, 13 stent) at the Helsinki Children's Hospital in 2000-2012. Characteristics, intervention and reintervention data were retrospectively collected from clinical records until 2014 (median follow-up 7.9 years). Age- and sex-matched comparisons between the treatment groups were performed in 86 patients (surgery n = 43, percutaneous n = 43).

Results: Forty of the 251 (16%) patients after surgery, 9/40 (23%) patients after balloon angioplasty and 4/13 (31%) patients after stent placement underwent a reintervention after a median time of 3.4, 11.7 and 19.5 months (P < 0.05), respectively. In the surgery group, all reinterventions occurred in children operated on ≤12 months of age and were related to lower body weight and smaller dimensions of the aorta. In the balloon angioplasty group, a higher post-procedure systolic arm-leg blood pressure gradient was associated with reintervention. After stent placement, three-fourths of the reinterventions were performed in a planned postinterventional catheterization. In the age- and sex-matched comparisons (median 5,7 years, range 0,5-17,6), post-procedure blood pressure gradients were higher (mean 10 vs 4 mmHg, P = 0.03), and reinterventions were more common (28%, 95% confidence interval 17-43 vs 2%, 95% confidence interval 0-12) in the percutaneous group compared to the surgery group.

Conclusions: Reinterventions after surgery in neonates were relatively common. In older children, percutaneous treatment carried a higher risk of reinterventions, which were mainly related to residual coarctation after primary treatment.
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http://dx.doi.org/10.1093/ejcts/ezy252DOI Listing
March 2019

A normal T cell receptor beta CDR3 length distribution in patients with APECED.

Cell Immunol 2015 Jun 23;295(2):99-104. Epub 2015 Mar 23.

Haartman Institute, Department of Bacteriology and Immunology, and Research Programs Unit, Immunobiology, University of Helsinki, PB 21, FIN-00014 University of Helsinki, Finland. Electronic address:

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in the AIRE gene. Murine studies suggest that AIRE controls thymic expression of tissue-restricted antigens, its absence allowing nonselected autoreactive cells to escape. We tested this in humans using the TCRβ CDR3 length repertoire as a surrogate of thymic selection, as it shortens during the process. Analysis of healthy thymuses showed an altogether 1.9 base pair shortening, starting at the CD4(+)CD8(+)CD3(low) stage and continuing until the CD4(+) subset, likely encompassing both the positive and negative selection. Comparison of five APECED patients with eight healthy controls showed a skewed repertoire with oligoclonal expansions in the patients' CD4(+) and CD8(+) populations. The average CDR3 length, however, was normal and unaffected by the skewing. This was also true of the hypothesized autoreactive CD8(+)CD45RA(+) population. We failed to detect a subset with an abnormally long CDR3 repertoire, as would be predicted by a failure in selection.
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http://dx.doi.org/10.1016/j.cellimm.2015.03.005DOI Listing
June 2015

Effect of timing and route of methylprednisolone administration during pediatric cardiac surgical procedures.

Ann Thorac Surg 2015 Jan 18;99(1):180-5. Epub 2014 Nov 18.

Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Meilahti Hospital, Helsinki University Central Hospital, Helsinki, Finland.

Background: We compared the antiinflammatory and cardioprotective effects of the two most common regimens of corticosteroid administration in pediatric cardiac surgical procedures: a single dose delivered either at anesthesia induction or by cardiopulmonary bypass (CPB) prime.

Methods: Forty-five children, aged between 1 and 18 months and undergoing ventricular septal or atrioventricular septal defect correction, were randomized in double-blind fashion into three groups. The anesthesia induction group received 30 mg/kg methylprednisolone intravenously after anesthesia induction, and the CPB-prime group received 30 mg/kg methylprednisolone by CPB circuit. The placebo group received saline solution. Plasma concentrations of methylprednisolone, interleukin (IL)-6, IL-8 and IL-10, and troponin were measured at anesthesia induction before the study drug, 30 minutes on CPB, after patients were weaned from CPB, and 6 hours after cessation of CPB.

Results: Equally high methylprednisolone concentrations were detected in both methylprednisolone groups, but the measured peak concentration occurred earlier in the induction group. Significantly lower IL-8 concentrations were observed just after patients were weaned from and 6 hours after CPB in the anesthesia induction group compared with the placebo (p = 0.002, p = 0.001) and prime groups (p = 0.003, p = 0.006). Significant reductions of troponin were detected in both methylprednisolone groups compared with placebo (induction, p = 0.001; prime, p = 0.002) 6 hours after patients were weaned from CPB.

Conclusions: Methylprednisolone administration at anesthesia induction was superior in terms of antiinflammatory action. Methylprednisolone administration in CPB-prime only a few minutes before aortic cross-clamping and cardioplegia resulted in mean troponin reductions similar to those of administration at anesthesia induction. Corticosteroids may have direct cardioprotective properties, as reported in experimental studies.
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http://dx.doi.org/10.1016/j.athoracsur.2014.08.042DOI Listing
January 2015

Resection of the stenotic segment with individually tailored anastomosis for symptomatic congenital tracheal stenosis in infants.

Eur J Cardiothorac Surg 2014 Jun 28;45(6):e215-9. Epub 2014 Mar 28.

Department of Paediatric Cardiac Surgery, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland

Objectives: To analyse retrospectively population-based results of congenital tracheal stenosis (CTS) repair in infants in Finland.

Methods: Data on infants who were operated on for CTS in Helsinki Children's Hospital between August 1988 and May 2013 were analysed retrospectively. Fibreoptic bronchoscopy was performed perioperatively and in follow-up of all the surviving patients. The median follow-up time was 7 (range 1-20) years.

Results: Thirteen infants were operated on for CTS. Resection of the stenotic segment with individually tailored anastomosis was used in 12 patients and slide tracheoplasty in 1 patient. The median age at the operation was 2.9 (range 0.2-19) months. Eight (62%) patients had associated cardiovascular defects, which were corrected during the same operation. The median length of stenosis was 35% (range 25-60%) of the total length of the trachea. The median length of time of postoperative mechanical ventilation was 10 (range 5-19) days. The median length of time of intensive care treatment was 15 (range 7-40) days. One patient died from hypoplastic lung tissue and fibrosis, and multiorgan failure. One patient required reoperation, and 3 other patients received balloon bronchodilatations postoperatively. There was no late mortality. All of the 12 survivors had a good outcome.

Conclusion: Resection with individually tailored anastomosis with up to 55% of the stenotic segment of the trachea presented a good long-term outcome.
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http://dx.doi.org/10.1093/ejcts/ezu113DOI Listing
June 2014

Prenatal diagnosis improves the postnatal cardiac function in a population-based cohort of infants with hypoplastic left heart syndrome.

J Am Soc Echocardiogr 2013 Sep 24;26(9):1073-9. Epub 2013 Jul 24.

Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland.

Background: Prenatal 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.

Methods: A 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.

Results: Prenatally 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).

Conclusions: A prenatal diagnosis of HLHS is associated with improved postnatal right ventricular function, reduced metabolic acidosis, and end-organ dysfunction.
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http://dx.doi.org/10.1016/j.echo.2013.05.005DOI Listing
September 2013

Outcome of pediatric heart transplantation recipients treated with ventricular assist device.

Pediatr Transplant 2013 Feb 28;17(1):73-9. Epub 2012 Nov 28.

Department of Pediatrics, Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

This study was conducted to evaluate the long-term prognosis of pediatric HTx patients treated with VAD before transplantation. The clinical data of six patients bridged to HTx with Berlin Heart EXCOR pediatric device were analyzed retrospectively. Information about graft function, CA results, and EMB findings as well as appearance DSA was collected. Also, information about growth and cognitive function was analyzed. These findings were compared with age-, gender-, and diagnosis-matched HTx patients. During the median follow-up time of four and half yr after HTx, the prognosis including graft function, number of rejection episodes, and incidence of coronary artery vasculopathy, growth and cognitive development did not differ between VAD-bridged HTx patients compared with control patients. In both groups, one patient developed positive DSA titer after HTx. Our single-center experience suggests that the prognosis of pediatric HTx patients treated with VAD before transplantation is not inferior to that of other HTx patients.
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http://dx.doi.org/10.1111/petr.12028DOI Listing
February 2013

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

Interact Cardiovasc Thorac Surg 2011 Feb 16;12(2):270-2. Epub 2010 Nov 16.

Department of Paediatric Cardiac Surgery, Hospital for Children and Adolescents, University of Helsinki, P.O.B. 281, 00029 Helsinki, Finland.

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.
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http://dx.doi.org/10.1510/icvts.2010.241448DOI Listing
February 2011

The air-leak test is not a good predictor of postextubation adverse events in children undergoing cardiac surgery.

J Cardiothorac Vasc Anesth 2007 Apr 19;21(2):197-202. Epub 2006 Apr 19.

Department of Anesthesia and Intensive Care, Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland.

Objective: The air-leak test is recommended as a method of assessing the appropriate size of an uncuffed endotracheal tube (ETT) in children. The authors' primary objective was to determine whether the air-leak test would predict adverse events and reintubations after the removal of the ETT in children who have undergone cardiac surgery.

Design: Prospective, observational, clinical study.

Setting: University tertiary care hospital.

Patients: Ninety-four children <10 years of age undergoing elective cardiac surgery requiring cardiopulmonary bypass surgery.

Interventions: The attending anesthesiologist assessed air-leak pressure after intubation in the operating room (OR). In addition, the air-leak test was performed in 42 patients before extubation in the pediatric intensive care unit (PICU). The incidence of adverse events and the number of failed extubations were recorded after removal of the ETT.

Measurements And Main Results: Eleven of the 94 patients were excluded from the study. Four (4.3%) of the patients died in the PICU before extubation, and 7 patients were excluded for other reasons. The median age of the 83 children was 0.9 years (range 0.01-9.6 years). The total incidences of postextubation adverse events and failed extubations were 30.1% and 8.4%, respectively. An audible air leak < or =25 cmH(2)O airway pressure during the OR phase or before removal of the ETT during the PICU recovery phase had no significant predictive value for the incidence of adverse events (p = 0.63) or reintubations (p = 1.0). The patients undergoing simple and complete operations compared with more complex and incomplete operations had significantly fewer postextubation adverse events (p = 0.03). Neonates did not have a higher risk for postextubation adverse events (p = 0.64) or reintubations (p = 0.26) than older children.

Conclusion: The air-leak test did not predict an increased risk for postextubation adverse events and reintubations in children undergoing elective congenital heart surgery.
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http://dx.doi.org/10.1053/j.jvca.2006.01.007DOI Listing
April 2007

Most human thymic and peripheral-blood CD4+ CD25+ regulatory T cells express 2 T-cell receptors.

Blood 2006 Dec 22;108(13):4063-70. Epub 2006 Aug 22.

Haartman Institute, Department of Immunology, PB21, 00014 University of Helsinki, Finland.

Lack of allelic exclusion in the T-cell receptor (TCR) alpha locus gives rise to 2 different TCRs in 10% to 30% of all mature T cells, but the significance of such dual specificity remains controversial. Here we show that human CD4+ CD25+ regulatory T (Treg) cells express 2 distinct Valpha chains and thus 2 TCRs at least 3 times as often as other T cells. Extrapolating from flow cytometric analysis using Valpha2-, Valpha12-, and Valpha24-specific monoclonal antibodies (mAbs), we estimated that between 50% and 99% of the CD25+ Treg cells were dual specific, as compared with about 20% of their CD25- counterparts. Moreover, both TCRs were equally capable of transmitting signals upon ligation. Cells with 2 TCRs also expressed more FOXP3, the Treg-cell lineage specification factor, than cells with a single TCR. Our findings suggest that expression of 2 TCRs favors differentiation to the Treg-cell lineage in humans and raise the question of the potential functional consequences of dual specificity.
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http://dx.doi.org/10.1182/blood-2006-04-016105DOI Listing
December 2006

Coronary sinus orifice atresia with left superior vena cava in patients with univentricular heart.

Ann Thorac Surg 2006 May;81(5):e16-7

Department of Pediatric Cardiac Surgery, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.

Two patients with hypoplastic left heart syndrome had coronary sinus orifice atresia with persistent left superior vena cava. Both patients underwent successfully coronary sinus unroofing. One underwent surgery at the time of the bidirectional Glenn procedure and the other before creation of a total cavopulmonary connection. According to our population-based database, 10.3% of patients with univentricular heart have persistent left superior vena cava, and 2.3% have associated coronary sinus orifice atresia. Our cases highlight the importance of recognizing this anomaly in patients with univentricular heart to avoid high coronary venous pressure, which is potentially lethal.
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http://dx.doi.org/10.1016/j.athoracsur.2006.01.064DOI Listing
May 2006

Increased DNA adducts in Barrett's esophagus and reflux-related esophageal malignancies.

Ann Med 2002 ;34(7-8):565-70

Department of Cardiothoracic Surgery (Section of General Thoracic and Esophageal Surgery), Helsinki University Central Hospital, Helsinki, Finland.

Background: DNA adduct formation can initiate carcinogenic processes.

Aim: To examine the pre-malignant condition of Barrett's esophagus by measuring the DNA adducts.

Methods: DNA adducts were measured in the proximal and distal esophagus of patients with Barrett's esophagus (n = 9), patients with adenocarcinoma in the distal esophagus/esophagogastric junction (n = 28), and in control group of patients (n = 8) using the 32-P-postlabeling method. The average levels of DNA adducts are expressed as mean adducts/10(9) nucleotides + standard error of the mean. RESULTS. The average DNA adduct levels in the distal esophagus were significantly higher in both the Barrett's esophagus (24.5 +/- 7.9) and the adenocarcinoma (12.0 + 3.0) than in the control patients (0.1 +/- 0.08), P < 0.001. In the proximal esophagus, the DNA adduct levels were approximately equal in the Barrett's esophagus (7.0 +/- 1.0) and in the adenocarcinoma group (6.4 +/- 0.65). However, the levels in the proximal esophagus in both groups were significantly higher than in the control group (2.1 +/- 0.67), P < 0.05.

Conclusions: Patients with Barrett's esophagus and patients with esophageal/esophagogastric junction adenocarcinoma had significantly more DNA adducts than the control group. These results support the current concept of the carcinogenic potential of chronic gastroesophageal reflux, and the pre-malignant condition of Barrett's esophagus.
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http://dx.doi.org/10.1080/078538902321117779DOI Listing
April 2003

Oxidative stress has a role in malignant transformation in Barrett's oesophagus.

Int J Cancer 2002 Dec;102(6):551-5

Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland.

Mechanisms underlying the development of oesophageal adenocarcinoma are poorly understood. To discover the role of oxidative stress and radical scavenger capacity in the malignant transformation of Barrett's oesophagus, we measured myeloperoxidase activity, superoxide dismutase activity, glutathione content and total aromatic DNA adducts. Mucosal specimens came from 52 patients in 6 groups: symptomatic gastro-oesophageal reflux disease (GORD) without and with endoscopic oesophagitis, Barrett's epithelium without and with dysplasia, adenocarcinoma in the oesophagus and controls. In the GORD-oesophagitis-metaplasia-dysplasia-adenocarcinoma sequence, glutathione content was progressively lower and myeloperoxidase activity higher than in controls, plateauing at Barrett's epithelium without dysplasia. Only in Barrett's epithelium with dysplasia was SOD activity significantly increased. In all patient groups, DNA adduct levels were significantly higher than the control level. Though these levels between patient groups did not differ significantly, the level was highest in Barrett's epithelium without dysplasia and progressively lower in Barrett's with dysplasia and adenocarcinoma. Pooled data showed a negative correlation between glutathione content and DNA adducts (-0.28, p = 0.05). Simultaneous formation of DNA adducts, increased myeloperoxidase-related oxidative stress, decreased antioxidant capacity (glutathione content) and the negative correlation between glutathione content and DNA adducts in the GORD-oesophagitis-metaplasia-dysplasia-adenocarcinoma sequence of Barrett's oesophagus indicate a role in the pathogenesis and malignant transformation related to oxidative stress.
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http://dx.doi.org/10.1002/ijc.10755DOI Listing
December 2002

Intussusception and spontaneous amputation of the esophagus.

J Thorac Cardiovasc Surg 2002 Jul;124(1):205-6

Department of Cardiothoracic Surgery, Section of General Thoracic and Esophageal Surgery, Helsinki University Hospital, PO Box 340, Haartmaninkatu 4, FIN-00029 HUS, Helsinki, Finland.

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http://dx.doi.org/10.1067/mtc.2002.122817DOI Listing
July 2002

Incipient angiogenesis in Barrett's epithelium and lymphangiogenesis in Barrett's adenocarcinoma.

J Clin Oncol 2002 Jul;20(13):2971-9

Cellular Signalling Group, Division of Biochemistry, Department of Biosciences, Viikki BioCenter, University of Helsinki, Finland.

Purpose: Barrett's esophagus (BE), a precancerous condition for Barrett's 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 Barrett's 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 Barrett's adenocarcinoma cells to infiltrate regular lymph nodes.

Patients And Methods: Fifteen surgically resected Barrett's dysplasia or adenocarcinoma patients were included. Immunohistochemistry and a modified whole mount analysis were used.

Results: The incipient angiogenesis originates from the pre-existing vascular network in the lamina propria and infiltrates Barrett's epithelium, giving its ominous salmon-red color. Barrett's 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.

Conclusion: BE 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 Barrett's 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.
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http://dx.doi.org/10.1200/JCO.2002.09.011DOI Listing
July 2002
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