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Introduction:  Gastroesophageal reflux disease (GERD) is a common morbidity after esophageal atresia (EA) repair, and the antireflux procedure (ARP) is a way of treating GERD symptoms. The aim of this study was to evaluate whether reflux index (Ri) and growth were improved by ARP., Materials and Methods:  Ninety-nine individuals with EA treated at the Queen Silvia Children's Hospital in Gothenburg, Sweden, between 1997 and 2010 were followed prospectively according to a structured care program. Twenty-four-hour pH-metry (Ri) and growth were studied at birth, then at 1, 7, and 15 years of age. All the patients included had reached 7 years of age., Results:  Preoperatively, Ri was significantly higher (32%) in the ARP than the non-ARP group (10%). Postoperatively, no difference was seen between the groups. However, at 7 and 15 years of age, Ri was significantly higher in the ARP group than in the non-ARP group. Weight (standard deviation scores) was significantly lower in the ARP group at 1 and 7 years of age when compared with the non-ARP group, but these differences were not seen at birth and at 15 years of age. In a multivariate analysis, only birth weight remained a significant factor for low weight at 7 years of age. At 15 years of age, no risk factors for low body weight were found., Conclusion:  In the long term, ARP is not effective in reducing GERD as measured as Ri in EA patients. The ARP group had significantly lower weight at 1 and 7 years of age than the non-ARP group, but this was not the case at the age of 15., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: This retrospective study aims to report treatment results in patients with long-gap esophageal atresia (LGEA), gross A + B type, and discuss the value of different clinical findings and physiological tests in the follow-up., Methods: This retrospective observational study comprises all patients with LGEA admitted to our department between 1995 and 2010., Results: A total of 16 patients were included. Their mean gestational age was 35(+2) weeks and their mean birth weight was 1,945 g (-2.5 standard deviation scores). No catch-up growth in height could be seen and they remained smaller than the average population during the study period. Gastrostomy was performed as the first surgical procedure. Overall, 11 of the 16 patients had a delayed primary anastomosis. Elongation of the distal esophageal segment was required in 3 of the 16 patients and a colonic interposition in 2 of the 16 patients. The median age at definitive surgery was 150 days. All the patients had gastroesophageal reflux after their definitive surgery. Three of the 16 patients required surgery due to aspiration and all 3 had a pathological lung clearance index (LCI) at multiple-breath washout (MBW). At the age of 1 or 7 years, the LCI was pathological in 4 of the 14 patients, and spirometry showed an obstruction in 9 of the 14 patients., Conclusion: LGEA is a severe congenital malformation, with severe morbidity. No mortality was seen. MBW could be a useful tool for the early detection of progressive pulmonary damage., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: For many years, esophageal atresia (EA) has been curable by surgery. However, severe respiratory morbidity and gastroesophageal reflux (GER) symptoms remain a problem in many patients. The purpose of this study was to describe respiratory and esophageal morbidity, esophageal function, and lung function, including the small airways, in patients with the most common type of the malformation (EA with a distal fistula)., Methods: The study comprised 26 children undergoing surgery for EA, who had performed respiratory and esophageal function studies at the age of 7 years in a follow-up program. The study design was retrospective analysis of both these 7-year functional investigations and esophageal and respiratory morbidity from birth to the age of 7 years, as documented in medical records. Pulmonary function was evaluated mainly by spirometry and multiple breath washout (MBW), whereas esophageal function was evaluated by 24-hour pH studies., Results: We found a high prevalence of both respiratory (69%) and esophageal (62%) morbidity between birth and 7 years among the EA children. Examination with MBW (peripheral airway function) revealed few abnormal results, whereas spirometry revealed high airway obstruction in half the children, which also correlated well with overall respiratory symptoms (p = 0.047), as well as recurrent pneumonias (p = 0.035). However, no association with GER symptoms was found. In addition, 46% of the children had GER according to pH measurements, which were correlated to clinical GER symptoms but not to respiratory symptoms., Conclusion: This study confirms a high prevalence of respiratory and esophageal morbidity. In terms of respiratory function, the high proportion with a spirometric abnormality indicated an associated developmental delay/dysfunction in the central airways, whereas the peripheral airways appeared to have normal function at this age. Tracheomalacia may explain the spirometric abnormalities, but this need to be studied in more detail., (Georg Thieme Verlag KG Stuttgart · New York.)

In order to improve the treatment of children born with long-gap esophageal atresia, a porcine model was developed for studying esophageal regrowth using a bridging graft composed of a silicone stented Biodesign mesh. The aim of the study was to investigate how leakage and contact between the native muscle and Biodesign mesh affected the early healing response. Resection of 3 cm of intrathoracic esophagus was performed in 10 newly weaned piglets. They were fed through a gastrostomy 8-10 days prior to sacrifice. In order to achieve nonleaking anastomoses, the silicone stent and suturing technique had to be adjusted between the first four and second six piglets. The technical adjustment decreased leakage. A nonleaking anastomosis could not be achieved when the native muscle layers were sewn less central on the bridging graft compared with the mucosa. If there was leakage, the inflammatory response increased, with islets of perivascular T-lymphocytes and infiltration of macrophages in the native muscle layers. In the bridging area, new vessels were seen in the submucosa in 9 of 10 piglets between 4 and 10 days after surgery. Smooth muscle cells also appeared to move from the cut muscle edges of both the muscularis mucosa and the lamina muscularis and were seen as a layer of several cells under newly formed mucosa. Double staining of the basal membrane of the ingrowing vessels and the pericytes showed that the basal membrane was thinner over some of the pericytes, but there was no accumulation of immature-looking cells in the submucosa of the bridging area. In this porcine model, where esophageal regrowth was studied by using a bridging graft composed of a silicone stented Biodesign mesh, we can conclude that leakage increased the inflammatory response in early healing. Ingrowth of new vessels was seen in the bridging area and movement of smooth muscle cells was found under newly formed mucosa., (Copyright © 2013 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: Oesophageal atresia (OA) is a congenital malformation that can lead to persistent respiratory symptoms in adulthood., Aim: To describe the prevalence of respiratory symptoms in adulthood in a population-based study of patients with repaired OA and to compare this with the prevalence in the general population., Methods: Of 80 patients operated for OA in Gothenburg in 1968-1983, 79 were located. The patients received a questionnaire on respiratory symptoms. Controls were 4979 gender- and age-matched subjects who answered the same questions., Results: The questionnaire was answered by 73 of 79 (92%) patients. Physician-diagnosed asthma was reported by 30% in the OA group vs 10% in the control group (OR 4.1; 95% CI 2.4-6.8), and recurrent wheeze in 29% vs 5.5% (OR 6.9; 4.1-11.6). Also wheeze during the last year, asthma medication, a long-standing cough, cough with sputum production and chronic bronchitis were significantly more common among the patients with OA. In contrast, there was no significant difference regarding risk factors for asthma. The prevalence of respiratory symptoms did not appear to decrease with age., Conclusion: A high prevalence of respiratory symptoms remains among adult patients with repaired OA. Many of the patients had an asthma diagnosis. However, asthma heredity or allergic rhinitis was not overrepresented., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Aim: Solid tumours constitute 40% of childhood malignancies. The Swedish Childhood Cancer Registry is population based and includes all children with cancer reported from the six paediatric oncology centres in Sweden. The aim was to investigate incidence and survival., Methods: We used the new WHO ICCC-3 for reclassification of the patients. Incidence and survival analyses were performed in the study population., Results: Two thousand four hundred and eighty-seven children (<15 years) were diagnosed with solid tumours in Sweden between 1983 and 2007. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 65.3 per million children. The survival rates at 10 years of follow-up have improved significantly when comparing the two time periods, 1983-1995 and 1995-2007 (76 vs. 82%; p < 0.01)., Conclusions: The mean annual incidence of solid tumours in children was 65.3/million and has been stable during the study period. Survival rates for solid tumours at 5, 10 and 20 years follow-up were 80, 79 and 76%, respectively., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Purpose: To investigate the use and subsequent healing of a silicone stented small intestinal submucosa (SIS) tube as a full-circumference replacement following surgical resection of the esophagus in piglets., Material and Methods: Three centimeters of the intrathoracic esophagus was replaced with a silicone stented SIS tube (Cook Medical) in 6 growing piglets. The esophageal stent was retained for 4 weeks. Esophageal dilations were performed, if needed, after stent removal., Results: The piglets were sacrificed 1-17 weeks after surgery. Recurrent dilations were needed after stent removal. Histology showed that the gap between the resection margins was filled with new loose connective tissue consisting of fibroblasts and few inflammatory cells. In this tissue, intense angiogenesis was seen at the early time points, which then gave way to the proliferation of immature-looking smooth-muscle-like cells in the submucosa, which appeared to stem from the pericytes of the ingrowing capillaries., Conclusions: Through using a stented SIS tube as a circumferential esophageal replacement in a piglet model, this study suggests that pericytes from ingrowing capillaries may play a role in the remodeling of the SIS mesh. It remains to be seen if this process gives a favorable end result because stricture formation after stent removal remains a problem., (Copyright © 2011 S. Karger AG, Basel.)

Systemic inflammation is induced during extracorporeal circulation, resulting in an increased bleeding tendency and endothelial cell activation. Lungs from seven piglets were perfused by autologous blood in an extracorporeal circuit, where the lungs and the left atrium were attached to polyvinyl chloride (PVC) tubings and the blood circulated by a roller pump. The trachea was intubated and attached to a ventilator. The lungs maintained good gas exchange, despite a slight increase in lactate levels. Plasma tPA increased slightly over time, suggesting endothelial cell activation. Activation of inflammatory systems was reflected in increased levels of plasma interleukin (IL)-6 and IL-10. A model for the study of lung endothelial activation during extracorporeal circulation has been shown to be reproducible. The lung tissue was shown to be capable of gas exchange and activation of endothelial cells and procedure-induced inflammation were noted.

There is no consensus on the treatment of congenital diaphragmatic hernia (CDH), and practice seems to vary between centres. The main purpose of the present study was to survey current practice in Scandinavia. Thirteen paediatric surgical centres serving a population of about 22 million were invited, and all participated. One questionnaire was completed at each centre. The questionnaire evaluated management following prenatal diagnosis, intensive care strategies, operative treatment, and long-term follow-up. Survival data (1995-1998) were available from 12 of 13 centres. Following prenatal diagnosis of CDH, vaginal delivery and maternal steroids were used at eight and six centres, respectively. All centres used high-frequency oscillation ventilation (HFOV), nitric oxide (NO), and surfactant comparatively often. Five centres had extracorporeal membrane oxygenation (ECMO) facilities, and four centres transferred ECMO candidates. The majority of centres (7/9) always tried HFOV before ECMO was instituted. Surgery was performed when the neonate was clinically stable (11/13) and when no signs of pulmonary hypertension were detected by echo-Doppler (6/13). The repair was performed by laparotomy at all centres and most commonly with nonabsorbable sutures (8/13). Thoracic drain was used routinely at seven centres. Long-term follow-up at a paediatric surgical centre was uncommon (3/13). Only three centres treated more than five CDH patients per year. Comparing survival in centres treating more than five with those treating five or fewer CDH patients per year, there was a tendency towards better survival in the higher-volume centres (72.4%) than in the centres with lower volume (58.7%), p =0.065.

Objective: During extracorporeal circulation, initial contact between blood and the artificial surface of the circuit induces an overall activation of the hemostatic system. The objective of this study was to investigate the combined effect of epoprostenol (PGI (2) ), nitric oxide (NO) and nafamostat mesilate (FUT-175, a serine protease inhibitor), on plasma coagulation and platelet activation during experimental long-term perfusion., Design: Two identical extracorporeal life support (ECLS) circuits were primed with fresh, heparinized human blood, and circulated for 24 h. FUT was given with a bolus dose of 85 mg/l blood at the initiation of the experiment and thereafter as a continuous infusion of 14 mg/l/h. PGI (2), at a rate of 2.4 microg/l/h, was also administered to the experimental circuit, and 120 ppm NO gas was added to the oxygenator sweep gas. The other circuit was used as a control., Results: Higher platelet count and platelet membrane expression of GPIb were found in the experimental circuits as compared with control circuits. The levels of thrombin/antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (F1 + 2) increased significantly over time in the control circuits but remained low in the experimental circuits. Plasma levels of plasminogen activator inhibitor 1 (PAI-1) decreased rapidly in both circuits but were higher in the control circuits at each time point studied., Conclusion: The activation of platelets and of the coagulation system encountered during extracorporeal perfusion is consistently inhibited by a combination of PGI (2), NO and FUT-175. The combination of these drugs appears to be more effective than each drug separately.

Treatment with extracorporeal membrane oxygenation ECMO) is associated with side effects, e.g., blood cell consumption and activation. Our group has earlier shown that nitric oxide administered as a gas reduces platelet consumption and activation. In the present work we have studied the effect of the NO-donor S-nitroso-glutathione GSNO) on platelets and leukocytes in an in vitro extracorporeal circuit. Two complete ECMO circuits were perfused with fresh heparinized human blood for 24 hours. GSNO was administered as a continuous infusion to one circuit at a rate of 0.7 mg/hour in four paired experiments and at a rate of 3.5 mg/hour in another four paired experiments. The other circuit was used as a control. Blood samples were withdrawn from both circuits before the start of the experiments and at 0.5, 1, 3, 12, and 24 hours of perfusion. The samples were analyzed for red blood cell count, leukocyte count, platelet count, platelet membrane expression of glycoproteins GP) Ib and GPIIb/IIIa, leukocyte membrane expression of cluster of differentiation CD) 11b/CD18, as well as plasma concentration of tumor necrosis factor TNF)-alpha, interleukin IL)-1beta, and IL-8. No difference in these parameters between the GSNO and the control circuit at any time point was assayed. In this study, no significant effect of GSNO on circulating platelets or leukocytes during experimental extracorporeal circulation could be shown.

Background/purpose: There is a lack of large contemporary studies on the management of congenital diaphragmatic hernia (CDH), and the prediction of mortality remains difficult. The aim of this study was to investigate the influence of perinatal factors on mortality rate in a contemporary multicenter study., Methods: The authors conducted a retrospective multicenter cohort study. Twelve of 13 Scandinavian pediatric surgical centers participated in the study. During a 4-year period (1995 through 1998) 195 children with CDH were included. The main endpoints were hospital mortality rate and total mortality rate (before 2001). Bivariate and multivariate survival analyses were performed using Kaplan-Meier plots, Log-rank test, and Cox regression., Results: Overall hospital mortality rate was 30%. Among 168 neonates with symptoms within 24 hours (early presenters) 35% died before discharge. All 61 deaths occurred in 157 neonates with symptoms within the first 2 hours of life. Among early presenters, 27% had prenatal ultrasound diagnosis, 26% were delivered by cesarean section, and 21% had associated major malformations. Bivariate analysis of early presenters showed increased risk of death in neonates with prenatal diagnosis, associated anomalies, right-sided diaphragmatic hernia (RCDH), low 1-minute and 5-minute Apgar scores, low birth weight, short gestational age, and cesarean delivery. Neonates with prenatal diagnosis were characterized by significantly lower Apgar scores, lower birth weight, and increased frequency of associated anomalies than those diagnosed after birth. Multivariate analysis found that prenatal diagnosis (P =.004), 1-minute Apgar (P =.001), and RCDH (P =.042) were independent predictors of total mortality rate., Conclusions: In a series of 195 CDH patients, all 61 deaths occurred in the 157 neonates presenting with symptoms within the first 2 hours of life. Prenatal diagnosis, 1-minute Apgar score, and RCDH were significant independent predictors of total mortality., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Objective: Extra corporeal circulation of human blood is used daily in lifesaving procedures such as open-heart surgery and extracorporeal membrane oxygenation (ECMO). But extracorporeal circulation also induces activation of various cascade reactions in the blood. The objective of this study was to evaluate the effects of hemofiltration on cytokine release and removal as well as on platelet activation and consumption., Material and Methods: Two complete ECMO systems, each of them holding a hollow fiber oxygenator, a bladder box, PVC tubing and a roller pump were perfused for 24 h with fresh, heparinized human blood. A hemofilter was added to one of the paired systems. Blood samples were collected from both circuits before start, and at 0.5, 1, 3, 12 and 24 h of perfusion. A total of 8 paired experiments was performed., Results: The plasma concentration of interleukin (IL)1beta, IL-6 and IL-8, as well as of IL-1 receptor antagonist (IL-1ra) increased over time in both systems, but consistently lower levels were observed in the filter circuits compared to the controls. Only minor parts of these cytokines could be assayed in the ultrafiltrate. No significant difference in platelet count and platelet membrane expression of glycoprotein Ib was observed between the circuits., Conclusions: By adding a hemofilter to the ECMO circuit, it is possible to reduce the plasma concentration of interleukins without significantly affecting platelet activation and consumption.

The purpose of this study was to compare blood cell activation during in vitro long-term perfusion using 2 parallel in vitro extracorporeal membrane oxygenation (ECMO) systems. We compared two substantially different perfusion systems, an assistance respiratoire extra corporelle (AREC) system on one hand, containing an AREC pump, silicon tubing, and a hollow-fiber oxygenator, and a centrifugal pump system, on the other hand, containing a Biomedicus centrifugal pump, PVC tubing, and a membrane oxygenator. We measured the platelet count using an automated blood cell counter. Platelet activation was evaluated using a flow cytometric technique for the platelet membrane expression of glycoproteins and ELISA for the plasma concentration of beta-thromboglobulin (beta-TG), a platelet specific protein released into the blood upon platelet activation. The neutrophil count was assayed using an automated blood cell counter and the plasma concentration of cytokines using an ELISA kit. A significant difference between the two systems was observed in terms of the platelet membrane expression of glycoprotein (GP)Ib (p=0.0001) and GPIIb/IIIa (p=0.0037), indicating a lower degree of platelet activation in the AREC system. The concentration of neutrophils was significantly lower in the centrifugal system (p=0.002) compared to the AREC system. The neutrophil membrane expression of CD11b was significantly lower (p=0.0067) in the AREC system, indicating a lower degree of neutrophil activation compared to the centrifugal pump system. A significantly lower degree of hemolysis, as expressed by plasma hemoglobin, was observed in the AREC pump system (p=0.0491). In conclusion, lower degrees of the platelet membrane expression of GPIb and GPIIb/IIIa and of the neutrophil membrane expression of CD11b were observed in the AREC system, indicating a lower degree of platelet and neutrophil activation in this system. No significant difference between the two systems as to the plasma concentration of interleukin (IL)-1beta, IL-6, or IL-8 could be recorded. Further studies are warranted to specify the role of each individual component of the two systems.

The objective of this study was to determine the degree of leukocyte activation, as measured by cytokine release, in circulating blood during experimental extracorporeal circulation. Complete in vitro extracorporeal membrane oxygenation (ECMO) circuits were used, and 9 experiments were performed. Whole blood stored at 37 degrees C was used as the control. Blood samples were withdrawn before the start of perfusion and at 24 h of perfusion. Statistically significant releases of interleukin (IL)-1beta, IL-8, and IL-1 receptor antagonist were observed in the perfusion circuits compared to both the control blood and baseline values. Also, increases in plasma tumor necrosis factor (TNF)alpha and IL-6 were seen after 24 h of perfusion although these changes did not reach statistical significance. These results indicate that extracorporeal circulation induced leukocyte activation and cytokine release. These reactions might, as an additional trauma, deteriorate the situation in an already severely ill patient. A search for methods to counteract this untoward activation seems warranted.

The objective of this study was to evaluate the effect of albumin priming on platelet consumption and activation during long-term perfusion. Two identical in vitro extracorporeal membrane oxygenation circuits were used; one was primed with Ringer's solution containing human serum albumin, the other with Ringer's solution only. Fresh heparinized human blood was pooled, divided between the two systems and circulated for 24 h at 37 degrees C. Platelet count, plasma concentration of betathromboglobulin (BTG), platelet membrane density of glycoprotein (GP) Ib and of GPIIb/IIIa were assayed before the start and at 0.5, 1, 3, 12 and 24 h of perfusion. In total, seven experiments were performed. We found that during the first hour of perfusion, slightly higher platelet counts (p = 0.058) and lower BTG values (p = 0.0005) were observed in the circuits primed with albumin, compared to the control circuits. No statistically significant differences were observed for the platelet membrane expression of GPIb and GPIIb/IIIa. We conclude that albumin priming appears to transiently prevent platelet consumption and activation during long-term perfusion.

Background: The extended use of cardiopulmonary bypass (CPB) in cardiac surgery is limited because of damage to blood which in adults has been assessed by alterations in blood cell rheology. Blood trauma assessment in children is difficult because of the restrictions in sample volume and frequency but needs to be established from time to time in order to study the tolerance to new surgical and extracorporeal techniques., Materials and Methods: Fourteen pediatric patients undergoing cardiac surgery with CPB for congenital heart disease corrections were studied. Whole blood, red blood cell and white blood cell rheology (filterability) were monitored before, during and after CPB using the St. George filtrometer that used small amounts of blood., Results: The results showed that all the rheologic parameters were altered during the blood trauma of CPB and were outside the reference values before, during and after CPB., Conclusions: This suggested that blood cell rheologic disturbances did not recover soon after CPB and this may be of interest in long term follow-up to understand responses and recovery patterns to disease and interventions associated with pediatric heart surgery using CPB.

Introduction: During extracorporeal circulation the contact between blood and the artificial surface of the circuit induces several changes in the hemostatic system. The objective of the present study was to assess the effect of a serine protease inhibitor--Nafamostat mesilate (FUT-175)--on coagulation and on platelets during experimental extracorporeal circulation., Methods: Two identical Extra Corporeal Life Support (ECLS) circuits were primed with fresh, heparinized human blood and circulated for 24 h. FUT-175 was added to one of the paired circuits and the other was used as a control. The following FUT-175 concentrations were employed: (1) 7.1 mg/l/h, (2) 14.2 mg/l/h, (3) 14.2 mg/l/h + 85.5 mg given as an initial bolus, (4) 28.5 mg/l/h + 171 mg given as an initial bolus. Blood samples were collected from the circuits before the start of the perfusion and at 0.5, 1, 3, 12, and 24 h of perfusion, and analysed for platelet count, plasma betathromboglobulin (beta-TG), platelet membrane glycoprotein (GP) Ib and GPIIb/IIIa expression, thrombin/antithrombin III complex (TAT), prothrombin fragment 1+2 (F1+2), fibrinogen, D-dimer, and plasminogen activator inhibitor 1 activity (PAI-1)., Results: Significantly higher platelet membrane GPIb expression and lower plasma beta-thromboglobulin levels were observed in the circuits holding FUT-175, suggesting a lower degree of platelet activation. Also, a reduced activation of the coagulation system was observed in the "FUT-circuits", as reflected by the levels of F1+2 and TAT, and the PAI-1 activity that was rapidly inactivated., Conclusion: FUT-175 reduces the activation of platelets and plasma coagulation in an in vitro ECLS model.

Background: Hemorrhage is a major complication experienced in 10% to 35% of neonates treated with extracorporeal life support (ECLS). The increased bleeding tendency is partly due to an ECLS-induced thrombocytopenia and impaired platelet function. In the present study, we evaluated the effect of nitric oxide on the ECLS-induced platelet consumption and activation., Methods: Two identical in vitro ECLS circuits were primed with fresh, heparin-treated human blood and circulated for 24 hours. Nitric oxide (15, 40, or 77 ppm) was added to one of the oxygenators in each pair. Eight paired experiments were performed. Platelet count, plasma beta-thromboglobulin, platelet serotonin content, plasma nitrate, plasma cyclic guanosine monophosphate, and platelet membrane glycoprotein Ib were assayed before the start and at 0.5, 1, 3, 12, and 24 hours of perfusion., Results: Plasma nitrate and plasma cyclic guanosine monophosphate levels were significantly higher in the nitric oxide circuits than in the control circuits (p < 0.01). Higher platelet counts (p < 0.01) and lower beta-thromboglobulin levels (p < 0.01) were observed in the nitric oxide circuits compared with the control circuits. However, no significant differences in platelet serotonin content or platelet membrane glycoprotein Ib density were noted between the circuits., Conclusions: Nitric oxide probably reduces platelet consumption and platelet activation during ECLS.

The aim of this study was to evaluate an in vitro model for investigation of platelet function parameters in an extracorporeal system. Two different perfusion pumps were compared, a roller pump (Polystan) and a centrifugal pump (Biomedicus). A continuous increase in glycoprotein (GP)1b-negative platelets was observed in both circuits. A marked increase of plasma beta-thromboglobulin thromboglobulin concentration and a decrease of the intracellular pool of serotonin was observed, indicating a marked release of alpha as well as of dense granules. The plasma concentration of glycocalicin increased in parallel with a reduced platelet surface expression of GP1b, suggesting that the loss of GP1b is caused by proteolysis rather than by a downregulation of this receptor protein. It is concluded that ECLS results in a pronounced platelet degranulation and causes changes of important membrane receptors which might explain some of the bleeding problems observed in patients treated with ECLS. No significant difference was noted between the roller pump and the centrifugal pump. Trial of strategies, e.g., protease inhibitors and nitric oxide to revert this untoward effect of ECLS are highly warranted.

Purpose: Cancer of the cervix uteri can be controlled by cytologic screening for the detection of precursor lesions, but such intervention remains unrealistic in many countries in which this cancer is common. The possibility of reducing mortality by earlier clinical detection, followed by basic therapy, has never been properly assessed., Patients and Methods: We compiled records of incident cases of invasive cancer of the cervix diagnosed in a defined area of Sweden from 1930 through 1990. In a cohort of 6,044 women, we analyzed temporal trends in incidence and survival by clinical stage and age at diagnosis. Generalized proportional hazards models were used to study several factors simultaneously and quantify the overall reduction in mortality., Results: For each successive stage at diagnosis, the overall risk of dying increased 2.5-fold (95% confidence interval [CI], 2.4 to 2.7). From 1930, a marked improvement in stage distribution was accompanied by increasing survival rates in stages I and II disease. These changes largely took place before the introduction of screening and external-beam radiation. The 10-year relative survival rate increased from 33% in the 1930s to approximately 55% in the 1950s and thereafter., Conclusion: Improvements in public and professional awareness of cervical cancer resulted in diagnoses at earlier clinical stages. The rate of cure in early stages improved when basic local treatment was introduced, but only little of the progress was attributable to the introduction of more advanced treatment technologies. These findings offer considerable hope for a substantial reduction in the mortality of cervical cancer without cytologic screening, even in countries with limited resources.

Seventy-one patients with epithelial ovarian cancer stage III (n = 56) or IV (n = 15) were treated with carboplatin 300 mg/m2, epirubicin 50 mg/m2 and cyclophosphamide 400 mg/m2 every fourth week. Patients clinically free of tumour after six courses (n = 58) underwent a second-look laparotomy. Seventeen patients were microscopically tumour-free (24% of all) and an additional 10 (14%) had only microscopic cancer. Median time to progression was 19 months. The median survival was 33 months and the estimated 5-year survival 27%. The toxicity was mainly haematological, with leukopenia WHO grade 3-4 seen in 88% and thrombocytopenia grade 3-4 in 42% of the patients. The gastrointestinal toxicity was mild and no renal toxicity was seen. This chemotherapy regimen was effective with acceptable toxicity and could be given on an out-patient basis. The possibility of increasing the efficacy and decreasing the toxicity was discussed.

Knowledge of reliable prognostic factors is essential in cancer treatment. Especially when intensified treatment is to be considered to improve the overall result, it is desirable to identify well-defined high-risk groups. In a prospective study DNA ploidy and S-phase fraction were measured in 88 patients with endometrial cancer stage I and II. Fresh tumor samples were analyzed using flow cytometry prior to treatment. Diploid tumors represented 84% of the cases, and aneuploid represented 16%. The mean S-phase fraction in diploid tumors was 10%, as compared with 22% in aneuploid tumors. The follow-up time was 5 years in all cases. The survival rate for patients with diploid tumors was 92% and for aneuploid tumors 36%. In the surviving patients, the mean S-phase fraction was 10.4%, a significant difference from 19.9% in the nonsurviving patients (P < 0.001). The highest mortality was found when aneuploidy was combined with an S-phase fraction over 20%, with only 11% survival for 5 years. In diploid tumors with an S-phase fraction below 20%, the survival rate was 92%. In a stepwise regression analysis, S-phase fraction was found to be of the most important prognostic value, followed by myometrial invasion and stage of the tumor and ploidy. Grade was not found to be of any important significance.

Coarctation of the aorta with critical hypoplasia of the aortic arch is a ductus dependent malformation-complex often combined with severe intracardiac malformations with a common denominator: there is a predominance of the pulmonary circulation and a flow restriction through the ascending aorta. Coarctation of the aorta with critical hypoplasia of the aortic arch may be looked upon as a malformation bordering on hypoplastic left heart syndrome. The degree of aortic arch hypoplasia seems to mirror the severity of the intracardiac malformation. The first objective in reconstructing these hearts is to create an unobstructed flow through the aortic arch. Resection of the coarcted segment combined with carotid flap plasty is a surgical alternative which fulfils this objective. We have used the technique in premature-born and severely ill neonates where one-step total correction was considered contraindicated. Thirteen neonates were operated upon, there were no cerebral consequences referable to the carotid artery ligation and no recoarctations.

Background: Cytologic screening can reduce mortality from cervical cancer by detection and removal of premalignant lesions. Conceivably, mortality is further reduced because more women with invasive disease are diagnosed at an earlier, curable stage. This hypothesis can be assessed in Sweden, where population-based screening programs were introduced successively over about a decade starting in 1964., Methods: Record linkages permitted complete follow-up through 1986 of all 17,377 patients with invasive cervical cancer diagnosed in Sweden from 1960 through 1984. We analyzed relative survival rates that describe the survival of patients after elimination of the effects of causes of death other than cancer of the cervix., Results: Prognosis improved substantially in patients younger than age 50 years at diagnosis; from 1960-1964 to 1980-1984, the 5-year relative survival rate increased from 69.8% to 88.8% at age 20-29 years, from 71.7% to 85.5% at age 30-39 years, and from 68.6% to 77.9% at age 40-49 years. The excess mortality was thus reduced by more than half in patients diagnosed when younger than 40 years. In contrast, only slight or no improvement was noted in those diagnosed at older ages when screening was less extensive. In all time periods, a strong association was found between older age at diagnosis and poorer prognosis., Conclusion: Although alternative explanations for our findings must be seriously considered, the most obvious interpretation is that cytologic screening reduces mortality from cervical cancer by earlier diagnosis of invasive disease.

Preserving the rheological properties of whole blood cells is vital for their smooth passage in the capillaries without causing blockage and disturbances in the microcirculation. To evaluate the effect of mechanical trauma on the rheology of white blood cells during prolonged perfusion with membrane oxygenation (PPMO), 16 in vitro experiments were conducted for 72 hours. The St George Carrimed Filtrometer was used to estimate the plasma white cell filtration rates (P-WFR). Also an in vitro estimation of the ability of individual cells to pass through capillaries, the white blood cell clogging rate (WBC-CR), the number of clogging particles (WBC-CP), the total white blood cell count (T-WBC) and two in vitro estimations to assess the effect of aggregates and stiff cells in blocking the microcirculation were performed. The traumatized white cells reduced their mean P-WFR by 37% +/- 9, 72% +/- 2 and 76% +/- 2 at 24, 48 and 72 hours respectively (p < 0.001). The mean WBC-CR was increased to 15.2 +/- 1.5, 32.6 +/- 2.2 and 40.3 +/- 8.3 x 10(2)%/ml at 24, 48 and 72 hours respectively (p < 0.001). The mean WBC-CP was increased to 6.6 +/- 1.5, 9.7 +/- 1.2 and 13.9 +/- 2.1 x 10(6)/ml at 24 hours (p < 0.05), 48 and 72 hours respectively (p < 0.001). The T-WBC was decreased to 55% +/- 0.3, 23% +/- 0.2 and 14% +/- 0.1 and 14% +/- 0.1 at 24, 48 and 72 hours respectively (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Background and Methods: In a prospective study, the 5-year survival of 57 patients with Stage II endometrial cancer was correlated to the estrogen (ER) and progesterone (PR) receptor concentrations using the dextran-coated charcoal (DCC) technique. The cutoff level was 3 fmol/mg of protein for ER and 6 fmol/mg of protein for PR., Results: An histopathologic examination of the tumor tissue samples before treatment demonstrated that 16% of the cases (9 patients) were well-differentiated (Grade 1), 45% (26 patients) moderately differentiated (Grade 2), and 39% (22 patients) poorly differentiated (Grade 3). Only 3 were ER negative, whereas 19 were PR negative. The mean concentrations for ER and PR were 106 and 162 fmol/mg of protein, respectively. All patients received standard treatment, including preoperative irradiation. The total 5-year survival rate was 82% (47 of 57 patients). Deep myometrial invasion was important in Grade 3, but not in Grades 1 and 2; in these two grades, all five patients with deep infiltration survived. There was a correlation between receptor concentration and grade, with a significant difference between Grades 1 and 2 versus Grade 3. All patients who were ER negative survived, as did all patients who were PR negative in Grades 1 and 2. Of the patients with Grade 3 disease who died, four of six (67%) were PR negative. Of the patients with Grade 3 disease who survived, 10 of 16 (63%) were PR negative., Conclusions: Patients who survived for 5 years did not have significantly different ER and PR concentrations than those who died. The mean ER and PR concentrations in patients who survived were 99 and 159 fmol/mg of protein, respectively, compared with 108 and 178 fmol/mg of protein, respectively, for those who died.

The chromosomes of 111 ovarian cancer patients were studied in G- and C-banded slides from peripheral blood lymphocyte (PBL) cultures for chromosome damage caused by chemotherapy and radiotherapy and for asymmetry of the constitutive heterochromatin of chromosomes 1, 9, and 16. We also monitored the survival of these patients to determine whether any secondary neoplasia induced by the therapy and report the findings of our investigations. Melphalan (MEL) was the only drug used in single-drug chemotherapy. The incidence of chromosome abnormalities in melphalan-treated cells (25%) was higher than in the control group (17%). The incidence of structural changes was also higher (10.5%) in the MEL-treated group than in controls (6%). After treatments with combinations of drugs, the incidence of structural changes remained at the same level (11%). In the patients receiving combined treatment with MEL and radiation, the rate of structural changes increased dramatically (24%). The overall rate of chromosome aberrations in this group was also higher (50%). Combination of two or more drugs and radiation produced only 14% structural chromosome changes. The overall rate of chromosome aberrations was also low (20%) in this group. Of 111 patients studied, only 33 were alive 6 years after initiation of the study. Of the surviving patients, eight had rearranged chromosomes in the first analysis. After 5 years, new blood samples were collected from these patients and chromosome analyses showed abnormal karyotypes in all eight patients. All chromosome abnormalities in the second analysis were completely unrelated to those in the first analysis, however. Whether the chromosome changes in the second analysis were due to therapy or to other unknown factors could not be determined. Data on C-banding and the distribution of inversions indicated that 91% of the patients had C-band heteromorphisms of chromosomes 1, 91% had heteromorphisms of chromosome 9, and 69% had heteromorphisms of chromosome 16. Furthermore, inversions were observed in chromosome 1 (41% of patients), chromosome 9 (28% of patients), and chromosome 16 (5% of patients).

Neonatal operations have improved the prognosis for newborn children with aortic coarctation. The 30-day mortality of 123 neonates with isolated coarctation of the aorta collected from nine series was found to be 0.8%. The subclavian flap angioplasty was the most frequently used surgical procedure in this collected series. This technique is relatively new, however, and many questions have yet to be answered. In this study we have done subclavian flap repair in newborn pigs and followed them up to adult ages. The pigs were killed 28 or 44 weeks postoperatively, and the aortas were reexamined. All flaps had grown symmetrically in width and length and parallel to the growth of the descending thoracic aorta. The flaps were macroscopically intact. Signs of degenerative processes were not found. The wall thickness of the subclavian flap increased by growth of the individual fibroelastic lamellar units in the tunica media. This adaptation to the increased wall stress occurred early in life. The wall strength of the flap also increased by thickening of the intimal layer. We conclude that the subclavian flap is well suited to function as a part of the aorta in adult life.

Critical aortic stenosis (CAOS) is not compatible with life when the ductus arteriosus closes. We have treated 11 consecutive cases with isolated CAOS. Symptom presentation was in the early neonatal period and diagnosis was made noninvasively at a mean age of 4 days. All were operated on with transventricular dilation (TVD) at a mean age of 4.7 days. There was no early mortality. There were two late deaths due to fibroelastosis. Both had the smallest aortic anulus diameter (5 mm). Two other patients had aortic root replacement, one at the age of 6.5 weeks due to intractable heart failure, and the other at the age of 3 months due to increasing gradient. In these two cases elective surgery was made possible by a successful TVD in the early neonatal period. TVD in this material was not associated with any early mortality, which makes this procedure a good alternative in the treatment of CAOS.

From a referral area comprising one-fifth of the Swedish female population we investigated possible risk factors for endometrial cancer (EC) in different age groups. Seventy-seven women aged 31-45 with EC were collected retrospectively, and 99 women aged 46-65 were consecutively collected. Both groups were compared to referents randomly selected from a population based study from the city of Göteborg. The referents consisted of 1746 women aged 39-65 years. All cases were studied by hospital record and 82% of the women aged 31-45 years and 85% of those aged 46-65 years were studied by an extensive questionnaire. Among the referents 1409 (81%) were investigated by the above-mentioned questionnaire. Hirsutism, increased body mass index (BMI) and hypertension were significantly more common in both EC groups compared to referents. Nulliparity and infertility were significantly more common in the young EC group. Referents used combined oral contraceptives significantly more often than women developing EC. There was, however, no difference between the groups with respect to the duration of medication with combined oral contraceptives. There was a significant negative correlation between cigarette smoking and the development of EC. These findings indicate that untreated ovarian dysfunction like that present in polycystic ovarian disease (PCO) with unopposed estrogen action on the endometrium is associated with EC in younger women, and that smoking may protect against EC by an 'anti-estrogenic' effect.

In a retrospective study, the 5-year survival in 190 patients with endometrial adenocarcinoma stage II was evaluated in relation to different preoperative radiotherapy techniques. In one group, group A, 111 patients received low dose rate radium to the cervix region and in a second group, group B, 79 patients received high dose rate 60Co treatment using the after-loading technique. Both groups received intracavitary radium using the standard Heyman technique. There were no statistically significant differences in survival, after correction for intercurrent disease, between the two groups. The overall 5-year survival corrected by intercurrent disease was 79% for group A and 80% for group B. The histological grade survival in group A was 94% in grade 1, 83% in grade 2, and 60% in grade 3 and in group B, 100% in grade 1, 80% in grade 2, and 59% in grade 3. A correlation was found between histological grade, uterine sound, and survival in both groups. Only in grade 3 was deep infiltration found to have a worse prognosis. No metastasis in regional lymph nodes was found, but distant metastasis was a problem in grade 3. A significant overrepresentation of nullipara could be found among the 190 patients and was pronounced for grade 1. Our results indicate that vaginal radium application can be replaced by high dose rate 60Co in the treatment of stage II endometrial adenocarcinoma, with no decrease in the 5-year survival rate.

Diagnostic curettage has for many years been the method of choice to diagnose endometrial cancer in women with postmenopausal bleeding. The costs for curettage performed today are huge, and approximately only 10% in this group of women will be diagnosed with endometrial cancer. Thus less expansive techniques to obtain endometrial samples have been evaluated, but all of them are invasive. The value of endovaginal ultrasonography for identifying endometrial abnormality in this group of women has not been evaluated until now. This study used endometrial thickness as measured by endovaginal ultrasonography as an indicator of endometrial abnormality. It was demonstrated in 205 women with postmenopausal bleeding that if the endometrium was less than 9 mm thick, no endometrial cancer was found at curettage. The mean endometrial thickness in those women with endometrial cancer was 18.2 +/- 6.2 mm as compared with 3.4 +/- 1.2 mm in those women with atrophic endometrium. If the cutoff limit for endometrial abnormality was 5 mm, the positive predictive value for identifying endometrial abnormality was 87.3%. If this limit had been used in this study, 70% of the curettage procedures could have been avoided.

A case of transitional cloacogenic carcinoma of the urethra in a 70-year-old woman is reported. Due to incomplete removal of the tumor and reluctancy to undergo extensive surgery, the patient also received external radiation and afterloading with cobalt-60. The patient is alive with no evidence of disease 7 years after the diagnosis, which may suggest that postoperative radiation as outlined should be considered in elderly women with urethral carcinoma.

The value of using CA 125 for screening of ovarian carcinoma is still under debate. It is important to be aware of possible physiological variation in serum levels of this antigen. This study aimed at finding out whether there were any differences in CA 125 levels in serum at different cycle day periods of fertile women and postmenopausal women. In 106 women, CA 125 and ovarian volume were measured at different cycle day periods and in postmenopausal women. The highest levels were found in cycle day (CD) 1-9, i.e. 22 units/ml and the lowest in postmenopausal women i.e. 6.7 units/ml. No correlation could be found between the CA 125 levels and ovarian volume as measured by vaginal sonography.

Paraplegia is a rare but much feared complication of corrective surgery for coarctation of the aorta. The problem was studied in 31 newborn pigs submitted to subclavian flap aortoplasty. The aortic cross-clamping time ranged from 9-25 min. Twenty-three piglets with clamping times 9-18 min were neurologically intact, whereas eight with aortic clamping for 18-25 min became paraplegic. The clinical implications for newborn children with symptomatic aortic coarctation are discussed with regard to these experimental findings.

Aberrations of the C-band region of chromosome no. 1 (1qh) were studied in 109 patients with ovarian cancer and 192 healthy subjects. The groups were compared for heterochromatin size variations, intrapair size asymmetry, and inversion. No significant correlation was found between the size of 1qh and ovarian cancer. Heterochromatin size asymmetry was estimated visually and determined by objective measurement of 1qh length or area; the methods show strong correlation. The measurements were normalised by comparison with the length or area of 16p or the entire chromosome no. 1. However, since good reliability was found by simply relating the 1qh size difference to the mean 1qh size, this was considered an appropriate and simpler method of normalisation. Asymmetry indices of length and area measurements correlated well, implying that the simpler method of length measurements can be readily used. 1qh asymmetry, measured objectively or estimated visually, was significantly increased in the cancer patient group. The incidence of C-band inversion was significantly increased in the patient group. Moreover, inversion increased significantly with increasing 1qh asymmetry.

The effect of subclavian flap angioplasty on the growth of the left front limb and on its collateral circulation was studied in 11 pigs. The left subclavian artery and its first branch, the costocervical trunk, were divided while the remaining three branches--the deep cervical, the vertebral and the internal thoracic artery--were preserved. Postoperative angiographies (5 pigs) showed that the blood supply to the left front limb was maintained through these three branches, which acted as collaterals, supplying blood in retrograde fashion. The left vertebral artery was seen to be the predominant collateral already on postoperative day 1. Four months later the diameter of the left vertebral artery had increased more than that of the contralateral (right) vertebral artery. Eight months postoperatively the size of both front legs (6 pigs) was the same. No signs of cerebral disturbance were seen. The clinical implications of the findings are discussed.

The fate of the subclavian flap in aortoplasty was studied and a new synthetic monofilament, absorbable vascular suture (polydioxanone, PDS) was evaluated. In 11 piglets submitted to the aortic repair, the diameter of the aortic arch and descending aorta and the length and width of the subclavian flap were measured. The aortoplasty was performed with a continuous running suture of 6/0 PDS. All the animals survived and grew normally. They were sacrificed 6-26 weeks postoperatively, when the mentioned variables were reestimated. No aortic narrowing was found and no suture material was detectable in the lumen. The subclavian flap had grown uniformly in length and width. Histologic examination showed evening of the inner surface by intimal proliferation and healing of the anastomoses. There was no sign of flap destruction and tissue reaction to PDS suture was minimal, indicating normal growth and viability in all parts of the flap. The suture material was absorbed 26 weeks postoperatively. Continuous suture with absorbable PDS seems to be a good alternative for repair of aortic coarctation in early infancy.

Muscle biopsies from the upper and the lower part of the body (m. deltoideus dx and m. vastus lat dx) were taken in young men, 17-28 years of age, who had been operated upon for coarctation of the aorta in childhood. Significant differences regarding SDH-activity and some muscle substrate levels were found, with higher values in the leg muscle. The same differences were found in ten healthy controls. It is concluded that arm and leg muscle differ in these respects but that the haemodynamic difference remaining after coarctectomy does not seem to influence this situation.