Evaluation of Microvascular Density in Glioblastomas in Relation to p53 and Ki67 Immunoexpression.

Glioblastoma is the most aggressive tumor in the central nervous system, with a survival rate of less than 15 months despite multimodal therapy. Tumor recurrence frequently occurs after removal. Tumoral angiogenesis, the formation of neovessels, has a positive impact on tumor progression and invasion, although there are controversial results in the specialized literature regarding its impact on survival. This study aims to correlate the immunoexpression of angiogenesis markers (CD34, CD105) with the proliferation index Ki67 and p53 in primary and secondary glioblastomas. This retrospective study included 54 patients diagnosed with glioblastoma at the Pathology Department of County Emergency Clinical Hospital Târgu Mureș. Microvascular density was determined using CD34 and CD105 antibodies, and the results were correlated with the immunoexpression of p53, IDH1, ATRX and Ki67. The number of neoformed blood vessels varied among cases, characterized by different shapes and calibers, with endothelial cells showing modified morphology and moderate to marked pleomorphism. Neovessels with a glomeruloid aspect, associated with intense positivity for CD34 or CD105 in endothelial cells, were observed, characteristic of glioblastomas. Mean microvascular density values were higher for the CD34 marker in all cases, though there were no statistically significant differences compared to CD105. Mutant IDH1 and ATRX glioblastomas, wild-type p53 glioblastomas, and those with a Ki67 index above 20% showed a more abundant microvascular density, with statistical correlations not reaching significance. This study highlighted a variety of percentage intervals of microvascular density in primary and secondary glioblastomas using immunohistochemical markers CD34 and CD105, respectively, with no statistically significant correlation between evaluated microvascular density and p53 or Ki67.

General Clinico-Pathological Characteristics in Glioblastomas in Correlation with p53 and Ki67.

Introduction: A glioblastoma is an intra-axial brain tumour of glial origin that belongs to the category of diffuse gliomas and is the most common malignant neoplasia of the central nervous system. The rate of survival at 5 years, from the moment of diagnosis, is not higher than 10%. Materials and methods: In this retrospective study, fifty-four patients diagnosed with glioblastoma, from the Pathology Department of the County Emergency Clinical Hospital of Târgu Mureș, between 2014 and 2017 were included. We studied the clinico-pathological data (age, gender, location, and laterality) and, respectively, the immunoexpression of p53, Ki67, ATRX, and IDH-1 proteins. Results: We observed a statistically significant association between the laterality of the tumour according to the age groups, with the localization on the right side being more frequent in the age group below 65 years of age, while the involvement of the left hemisphere was more prevalent in those over 65 years. Out of the total 54 cases, 87.04% were found to be primary glioblastomas; more than 70% of the cases were ATRX immunopositive; almost 80% of the glioblastomas studied had wild-type p53 profile; and 35% of the cases were found to have a Ki67 index greater than 20%. A statistically significant association between gender and ATRX mutation was found; female cases were ATRX immunopositive in 92% of the cases. Almost 70% of the cases were both IDH-1 and p53 wild-type, and we observed the presence of both mutations in only 3.7% of the cases. Approximately 83% of primary glioblastomas were ATRX positive, respectively, and all IDH-1 mutant cases were ATRX negative. Conclusions: Glioblastomas still represent a multidisciplinary challenge considering their reserved prognosis. In this study, we described the most common clinico-pathological characteristics and IHC marker expression profiles, highlighting a variety of percentage ranges in primary and secondary glioblastomas. Given the small number of studied cases, further prospective studies on larger cohorts are needed in the future to evaluate the role of these immunohistochemical markers as prognostic factors for survival or recurrence.

The immunoexpression of aquaporin 1, PAX2, PAX8, connexin 36, connexin 43 in human fetal kidney.

INTRODUCTION: The kidney develops from two mesodermal primordia. Aquaporin 1 (AQP1) is a membrane protein characteristic to epithelial and endothelial cell of the human body. The Pax family of genes encodes transcription factors with important role in intrauterine development. Connexins are transmembrane proteins found in gap junctions. We monitored the changes in the expression of AQP1, paired box gene 2 (PAX2), paired box gene 8 (PAX8), connexin 36 (Cx36) and connexin 43 (Cx43) proteins in fetal renal tissue. MATERIALS AND METHODS: We studied 34 post mortem fetuses of 9 to 24 weeks from the Laboratory of Pathology, Emergency County Hospital of Târgu Mures, Romania, using immunohistochemistry. RESULTS: AQP1 expression appeared in the apical and basolateral parts of cells, lining the proximal convoluted tubules and the descending limb of Henle's loop, then in the tubule pole of Bowman's capsule also. Nuclear expression of PAX2 was observed in structures developed both from the ureteric bud and the metanephric mesenchyme, and of PAX8 was observed in the proximal convoluted tubule's epithelium, Henle's loop, and collecting ducts. Cytoplasmic expression of Cx36 was localized to nephrons in different developmental stages, glomerular vessels and collecting ducts, and of Cx43 was localized to the endothelium of glomerular and peritubular vessels, as well as to the epithelium of the proximal tubules. DISCUSSIONS AND CONCLUSIONS: Nephrogenesis begins in the embryonic period, and continues into the fetal period as well. It is regulated by a wide array of markers. The current study supplements literature data regarding immunoexpression of these markers during renal development in the fetal period.

Virtual museum of congenital heart defects: digitization and establishment of a database for cardiac specimens.

Education and training of morphology for medical students, and professionals specializing in pediatric cardiology and surgery has traditionally been based on hands-on encounter with congenitally malformed cardiac specimens. Large international archives are no longer widely available due to stricter data protection rules, a reduced number of autopsies, attrition rate of existing specimens, and most importantly due to a higher survival rate of patients. Our Cardiac Archive houses about 400 cardiac specimens with congenital heart disease. The collection spans almost 60 years and thus goes back to pre-surgical era. Unfortunately, attrition rate due to desiccation has led to an increased natural decay in recent years. The present multi-institutional project focuses on saving the collection by digitization. Specimens are scanned by high-resolution micro-CT/MRI. Virtual 3D-models are segmented and a comprehensive database is built. We now report an initial feasibility study with six test specimens that provided promising results, however, adequate presentation of the intracardiac anatomy, including septa and cardiac valves requires further refinements. Computer assisted design methods are necessary to overcome consequences of pathological examination, shrinkage and/or distortion of the specimens. For a next step, we anticipate an expandable web-based virtual museum with interactive reference and training tools. Web access for professional third parties will be provided by registration/subscription. In a future phase, segmental wall motion data could be added to virtual models. 3D-printed models may replace actual specimens and serve as hands-on surgical training to elucidate complex morphologies, promote surgical emulation, and extract more accurate procedural knowledge based on such a collection.

Late endocarditis of Amplatzer atrial septal occluder device in a child.

Bacterial endocarditis following atrial septal defect closure using Amplatzer device in a child is extremely rare. We report a 10-year-old girl who developed late bacterial endocarditis, 6 years after placement of an Amplatzer atrial septal occluder device. Successful explantation of the device and repair of the resultant septal defect was carried out using a homograft patch. The rare occurrence of this entity prompted us to highlight the importance of long-term follow up, review the management and explore preventive strategies for similar patients who have multiple co-morbidities and a cardiac device. A high index of suspicion is warranted particularly in pediatric patients.

[Primary, single-stage arterial switch operations at a newly-established, comprehensive congenital cardiac center performed in the neonatal age and beyond]. / Újszülöttkorban és késobb végzett primer artériás switchmutétek eredményei egy újonnan létrehozott, átfogó congenitalis szívközpontban.

INTRODUCTION: Outcome of arterial switch operation for transposition of the great arteries with/without ventricular septal defect is a service key-performance-indicator. AIM: The aim of the authors was to assess patient characteristics and parameters in the perioperative course. METHOD: In the setting of a newly-established, comprehensive tertiary-care center, primary complete repair was performed including associated anomalies, e.g. transverse arch repairs. Patients with d-transposition were grouped according to coexistence of ventricular septal defect. RESULTS: 118 arterial switch operations were performed between 2007 and 2014 with 96.62% survival (114/118). Ventricular septal defect and repair of associated anomalies did not yield worse outcome. Left ventricular re-training with late presentation necessitated mechanical circulatory support for 4.5±1.5 days. CONCLUSIONS: D-transposition is suitable for standardization of clinical algorithm and surgical technique. Quality standards contribute to excellent outcomes, minimize complications, and serve as blueprint for other neonatal open-heart procedures. Availability of mechanical circulatory support is key for single-stage left ventricular re-training beyond the neonatal period.

Large cardiac fibroma and teratoma in children- case reports.

Primary cardiac tumours in paediatric population are an unusual occurrence. Although, majority of such tumours are benign (90%), the frequency and type of cardiac tumours in this age group is different from the adult population. There are several consecutive series published in the last decade on cardiac neoplasms. Therefore, this is not only an effort to contribute to the existing literature for better understanding and management of similar patients but also to highlight the importance of early detection either by prenatal imaging or careful evaluation of differential diagnosis of common symptoms. We herein, describe two infants with large cardiac tumours (fibroma and teratoma) both arising from the interventricular septum and underwent surgical excision. A possible role of cardiac remodeling in myocardial tissue healing after extensive tissue resection in such patients is hypothesised through available experimental or limited clinical information.

[Surgical management of congenital heart defects in adolescent and adult patients, between years 2001-2008]. / Tapasztalataink a fiatal- és felnottkori veleszületett szívhibák sebészi kezelésében 2001-2008.

UNLABELLED: The leading interventions due to congenital heart defects performed in adults are: (I) reconstructive operations, including: (a) newly diagnosed malformations, (b) previously adjudged to be inoperable defects, (c) so called "tardive" interventions due to pulmonary hypertension or right ventricle insufficiency. There is a growing number of (II) REDO operations, including: (a) correction of residual defects, (b) replacement of damaged or outgrown homografts, (c) recoarctation (aneurysm, dissection) of the aorta after surgical or catheter interventions, (d) Ross procedure, valve replacements due to previously performed aortic valvulotomy/valvuloplasty or corrections of different malformations (e.g. TGA). PATIENTS AND RESULTS: 166 of all 4496 operations were performed in adolescents and adults (age: 16-52 years, mean: 28 years) between years 2001-2008. The distribution of these interventions: Ia: 77, Ib: 15, Ic: 4, IIa: 11, IIb: 22, IIc: 9, IId: 28. Mortality rates were the following: 0 intraoperative, 4 early postoperative, 1 pulmonary hypertensive crisis, 1 malignant rhythm disturbances, 2 multi-organ failure. CONCLUSIONS: The main risk factors are pulmonary hypertension and right ventricle failure. Complex surgical solutions do not mean extreme problems for a congenital cardiac surgeon, but earlier diagnosis and the use of ECMO during therapy may improve the results.

[Anatomic correction of the congenitally corrected transposition of the great vessels by the first successful "double switch" operation in Hungary]. / Korrigált nagyér-transzpozíció anatómiai korrekciója ("double switch"). Elso sikeres hazai mutéti megoldás.

Congenitally corrected transposition of the great arteries is a rare defect characterized by discordant atrioventricular and ventriculoarterial connections. Symptoms result from one or a combination of associated cardiovascular malformations, including ventricular septal defect, pulmonary stenosis or atresia, tricuspid valve dysfunction, dextrocardia, hypoplastic left or right ventricle. Correcting exclusively the associated defects, leaving the morphologic right ventricle in systemic position, will determine the patient's life-long prognosis. Anatomic repair by double switch technique may improve survival of patients with congenitally corrected transposition of the great arteries by establishing the morphologic left ventricle in the systemic circulation. A 3-year-old girl with congenitally corrected transposition of the great arteries, ventricular septal defect, hypoplastic right ventricle, and previous palliative procedure was corrected by double switch technique and patch closure of ventricular septal defect. The authors prefer the double switch procedure inspite of its many surgical challenges because it has very good long-term outcome. The more simple surgery namely the operation of only associated cardiac defects will involve the possibility of deterioration of right ventricular function.

[Challenges in the surgical management of hearts with a functional single ventricle]. / Kihívások az egykamrás komplex veleszületett szívhibák sebészi kezelésében.

UNLABELLED: Nowadays, the complex congenital heart diseases with a functional single ventricular haemodynamics can be treated with good results with bi-directional Glenn (BDG) and total cavopulmonary connection (TCPC) procedure. The late results are determined by the ventricular function. AIMS: To assess the surgical results of "high risk" BDG and TCPC procedures, where the functional single ventricle were complicated by left sided SVS and IVC, total anomalous pulmonary venous connection (TAPVC) and severe atrioventricular valve insufficiency. These patients' were refused for surgery earlier. PATIENTS: Between 01. 01. 1994. and 30. 06. 2004. 112 BDG and 93 TCPC (42 pts with extracardiac conduit--ECC) procedures were performed. AGE: 3 months-29 yrs mean: 4,7 yrs, weight: 4-46 kg, mean: 15,5 kg. Among the "high risk" pts.: 1. Bilateral BDG in 19, left BDG in 9, left sided TCPC with ECC in 3 pts. were performed, 2. The associated TAPVC were operated on successfully in 3 pts. (bilateral BDG in 1, left BDG in 1, left sided TCPC with ECC in 1), 3. Mitral valvuloplasty in 2, artificial (mitral) valve implantation in 1, tricuspid valve closure or valvuloplasty in 3, (tricuspid) valve replacement in 1, common AV valve replacement in 1 pts were performed, 4. In 4 infants BDG was performed after Norwood I. procedure. RESULTS: Five pts. were lost after BDG procedure (Damous-Kaye-Stansen operation were performed as well in 3 pts.), and another 5 patients' systemic pulmonary shunts were re-done. Four patients after TCPC were lost and reoperation to BDG (n = 1) or shunt procedure (n = 2) was performed in 3 pts. Pre-discharge echocardiography confirmed mitral valvuloplasty with good results. No intervention was necessary in the follow up (1-3 yrs period) due to AV insufficiency and ventricular functions improved. CONCLUSION: On the basis of our series the "high risk" BDG and TCPC operations can be performed with an encouraging early result. The authors previously contraindicated associated defects can be surgically managed. Our short and mid-term results are feasible in this aspect. The long-term control of the "uni-ventricular" heart's ventricular function needs further investigation.

[Right subaxillary and posterolateral thoracotomy for open repair of congenital heart defects]. / Jobb oldali subaxillaris és posterolateralis thoracotomia alkalmazása veleszületett szívhibák nyitott szívmutétei során.

OBJECTIVE: Low-risk cardiac surgery approaches zero morbidity/mortality, therefore, cosmetic issues append. Right thoracotomy has been advocated as cosmetically attractive alternative to median sternotomy. Posterolateral thoracotomy involves chest wall musculature division that contributes to postoperative pain/morbidity; access to the heart may be difficult. Longitudinal subaxillary incision and muscle-sparing thoracotomy can overcome these disadvantages and provide better visibility. PATIENTS AND METHODS: Between April 2000 and April 2004 the authors performed open-heart repair from right thoracotomy in 161 patients. Diagnoses comprised perioval and sinus venosus ASDs (137), VSD (11), incomplete/intermediate AVD (8), miscellaneae (5). According to both patients' and surgeon's preference a longitudinal midaxillary incision and muscle-sparing lateral thoracotomy was utilised in 98 cases. Intracardiac repair was performed by extracorporal circulation, usual cannnulation, cardioplegia. Data of 79 ASD closures via midline sternotomy were used as controls. RESULTS: Sternotomy and thoracotomy groups did not differ in demographic characteristics albeit thoracotomies exhibited wider age and weight range. The skin incision could be easily stretched up by 60% providing excellent visibility/access. No mortality occurred. Phrenic nerve palsies (2), transient tetraparesis (1) fully recovered. A mitral valve replacement was necessary for valve pathology unrelated to access. No breast and/or upper limb vascular/neurologic problems were encountered. CONCLUSIONS: Right subaxillary muscle-sparing thoracotomy offers safe option for open-heart repair of selected anomalies. Despite the shorter skin incision subaxillary approach provides better visibility than conventional thoracotomy as mediastinal organs are closer to the operator. Intermediate cosmetic result are appealing. With no muscles divided less postoperative pain is anticipated. The authors recommend to expand the spectrum of anomalies repaired via this approach.

[Surgical management of preterm infants and low birth weight neonates with congenital heart disease]. / Veleszületett szívhibák sebészete koraszülötteken es kis súlyú ujszülötteken.

UNLABELLED: Nowadays, due to the development of cardiac surgery, pediatric cardiology and anesthesia, almost every congenital heart disease can be corrected totally or partially. The increasing number of surgical corrections will lead to better life quality. The surgical mortality has decreased significantly, even in the most complex cases. Only few cases can not be treated surgically. The aim of this study was to examine these positive changes, what they mean in the treatment of premature babies with congenital heart disease. These patients are endangered because of their age as well, they require special treatment and the surgical treatment has always meant high risk, urgent interventions. PATIENTS: between 01. 01. 1975. and 31. 12. 2003. 447 premature babies were operated on. The patients were divided into 3 subgroups by their weight: I: 470-1500 gr. - 19 patients, II: 1500-2000 gr. - 93 pts., IIl: > 2000 gr. - 335 pts. There were 69 corrective surgical procedures performed mainly after 1998. RESULTS: Overall early mortality: 81 patients (18.1%). Detailed mortality: group I.: 0%, group 11: 23 (24.7%), group III.: 58 (17.3%). The early mortality reduced from 21.6% to 6.3% (closed procedure), and 27.7% to 10.8% (ECC operation). The successful operations in the smallest weight groups were as follows: On ECC: Total Anomalous Pulmonary Venous Return (1600 g), Transposition of the Great Arteries--Arterial Switch (1800 g), Ventricular Septal Defect (1800 g), Aortopulmonary fenestration (2000 g), Hypoplastic Left Heart Syndrome-Norwood procedure (2200), AV septal defect (2300 g), Interrupted aortic arch + Ventricular Septal Defect (2300 g), Truncus arteriosus (2500 g). Without ECC: Coarctation of the aorta (930 g), Patent Ductus Arteriosus (470 g). CONCLUSION: Nowadays the possibilities and the chances of the corrective procedures of congenital heart diseases in those patients with bodyweight of over 2000 g and in those that are mature babies are the same. In those patients with bodyweight 1500-2000 g procedures without ECC had good results, on-pump procedures had higher mortality rate, but the long-term results were acceptable. At the moment only procedures without ECC are performed on babies with weight under 1500 g--but with higher risk. Our effort is to perform ECC operations in patients with bodyweight less than 1500 g.

[New strategies in surgical management of coarctation of the aorta 1975-2001]. / Szemléletváltozás a coarctatio aortae sebészi kezelésében 1975-2001.

AIM: This article presents the early and late surgical results of 401 newborns and infants among the 569 children with coarctation of aorta who were operated on between 1975-2001. RESULTS: The early results were dependent on the anatomy of the aortic arch, the age and weight of babies and the types of the associated heart defects. The mortality rate was reduced from 15% (isolated coarctation 7.3%, complex coarctation 34%) to 3.0% (isolated 1.9%, complex 4.9%). 77.3% of 320 infants (follow-up 1 month-26 years, mean: 17 years) were free from re-operation or intervention. The (extended) end-to-end anastomosis and the subclavian flap method produced the best surgical results. CONCLUSIONS: They suggest the extended end to end anastomosis technique for repair of the aortic arch together with the reconstruction of the associated heart defects in the youngest age if it is possible. The balloon angioplasty of the recoarctation of the aorta produces a good result.