Vol. 60 No. 2, April-June 2019

1. Do we know enough about the genetic involvement in laryngeal cancer susceptibility and prognostic outcome?

Corina Iulia Cornean, Marcel Cosgarea, Andreea Catana, Carmen Aurelia Mogoanta, Violeta Necula, Alma Aurelia Maniu

Introduction: Advances in molecular biology have opened the door to a wide range of research material through the usage of genetic testing on certain variables within the human genome known as single-nucleotide polymorphisms (SNPs).The purpose of this article is to present a review on the influence variants within SNPs have on the outcome of laryngeal cancer when associated with different variables, such as external toxins or survival rate. Amongst these toxins, the most frequent and most studied have been alcohol and tobacco consumption, with a proven increased rate of overall cancer risk within the aero-digestive tract. Materials and Methods: The review was realized utilizing available studies on the subject of genetic polymorphisms analysis of deoxyribonucleic acid (DNA) samples using polymerase chain reaction (PCR) assays and laryngeal cancer published in the PubMed database. Results: Statistical analysis of 262 polymorphisms shows a predominantly positive association between two genetic variants of the human genome (mutant homozygote and heterozygote) and cancer risk with significant influence on patient outcome and survival. Genotype combinations were divided into two categories depending on the individual at risk and protective allele within the loci of each inherited gene block. Amongst the genes involved with aero-digestive cancers, the most studied were those belonging to the xenobiotic metabolism, nucleotide excision repair (NER) and DNA repair pathways. The presence of toxins has a distinct cumulative effect within the genotype-phenotype relationship, which further influences the presence of malignancy depending on the adaptability of each individual genome. Conclusions: Laryngeal cancer evolution is linked to inherited risk factors found within the genetic code. Most studied were the genes belonging to NER pathways, DNA repair and xenobiotic metabolism, which all favored mutant homozygote and heterozygote variants, as high risk factors. Only five articles focused on overall survival rates with insufficient results to undisputedly predict the risk variants. The consumption of external toxins has a positive effect on the overall cancer risk in consumers. Most articles affirmed further evaluation or replication was needed in a larger scale population to conclusively validate their results.

Corresponding author: Carmen Aurelia Mogoanta, Senior Lecturer, MD, PhD; e-mail:; Violeta Necula, Senior Lecturer, MD, PhD; e-mail:

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2. Protean cytological, histological and immunohistochemical appearances of medullary thyroid carcinoma: current updates

Catalin Mihai Buzduga, Claudia Florida Costea, Alexandru Carauleanu, Ludmila Lozneanu, Mihaela Dana Turliuc, Andrei Ionut Cucu, Manuela Ciocoiu, Mariana Floria, Daniela Maria Tanase, Raluca Alina Dragomir, Raluca Maria Haba, Ana Maria Dumitrescu, Camelia Margareta Bogdanici, Delia Gabriela Ciobanu Apostol

Medullary thyroid carcinoma (MTC) accounts for only 0.5-3% of all malignant diseases, but is responsible for more deaths every year than all the other endocrine malignancies taken together. Approximately 75-80% of MTCs occur sporadically, while the inherited forms of MTC are responsible for the rest of the cases. The heritable MTC results from a germline mutation in the rearranged during transfection (RET) proto-oncogene and is included into the multiple endocrine neoplasia 2 (MEN2), being associated with other endocrine abnormalities and clinical features. MTC is a neuroendocrine tumor that releases a wide range of secretory products that are responsible for a variety of symptoms, making it difficult to be diagnosed. For this reason, the pathological analysis is of vital importance to ensure that the correct diagnosis is made. This review presents the main data from the contemporary literature related to the pathological diagnosis of a patient with MTC and highlights the wide range of tumor cytological features, the many histological variants, as well as the particular tumor immunophenotype. It also reveals the new approach to this type of cancer in the new World Health Organization (WHO) Classification of Thyroid Tumors (2017) and the reassessment of MTC tumor category in the new American Joint Committee on Cancer/Tumor, Node, Metastasis (AJCC/TNM) Staging (2017).

Corresponding author: : Claudia Florida Costea, Senior Lecturer, MD, PhD; e-mail:; Alexandru Carauleanu, Senior Lecturer, MD, PhD; e-mail:

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3. Antiplatelet therapy in secondary ischemic stroke prevention - a short review

Cristina Florescu, Edme Roxana Mustafa, Elena-Anca Tartea, Diana-Ruxandra Florescu, Valeria-Carmen Albu

Platelets play an essential role in atherothrombosis and for this reason they are the primary target of antithrombotic therapy in ischemic stroke. We discussed here the evidence for efficacy and safety of current knowledge in antiplatelet therapy for stroke prevention after an acute ischemic stroke or transient ischemic attack. After an acute episode, long-term antithrombotic therapy is essential for the secondary prevention of stroke recurrence and complications. Antiplatelet therapy for acute ischemic stroke (non-cardioembolic) or ischemic stroke consists of three antiplatelet drugs, in accordance with Food and Drug Administration (FDA) from the USA and also with the Guidelines published by the American Heart Association (AHA) and nevertheless with the Guidelines of the American Stroke Association (ASA), in 2014, for preventing vascular events, such as stroke. These are aspirin, clopidogrel and dipyridamole. Moreover, recent randomized clinical trials and the last Guidelines for stroke of AHA/ASA, in 2018, also mention ticagrelor. All of these antiplatelet therapies, besides inhibiting acute arterial thrombosis, also interfere with physiological hemostasis. In conclusion, we can say that current recommendations focused primarily on the therapy with aspirin for the secondary prevention of stroke in patients that presented vascular events, such as ischemic stroke of non-cardioembolic cause or transient ischemic attack and, as appropriate, aspirin plus dipyridamol or clopidogrel. The new therapy with ticagrelor in secondary stroke prevention seems to be promising, but more randomized clinical trials are needed to accurately assess the safety and efficacy of this new antiplatelet drug.

Corresponding author: Elena-Anca Tartea, MD, PhD; e-mail:

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4. Current understanding of psycho-neurobiology in depressive disorders with suicidal thoughts - translational models

Eduard Nicusor Bondoc, Dragos Marinescu, Ileana Marinescu, Ramona Denise Malin, Liliana Stanca, Roxana Eugenia Zavoi

Epidemiological data confirm the rising incidence of depression associated with suicidal ideation and cardiovascular comorbidities of coronary type. In contradiction with the large number of antidepressant drugs, the therapeutic results are not satisfactory, with numerous existing incomplete remissions characterized by maintained cellular dysfunctionalities that amplify the cognitive deterioration and the risk of several somatic comorbidities. The surprising fact is the relatively high number of deaths in this type of patients due to acute coronary disease (myocardial infarction - MI). The vulnerability of hippocampal and frontal cortex cerebral structures is presented as obtained on animal model consecutive to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and on theoretical model where the hypothalamic disconnectivity determines the activation in the sympathetic autonomic nervous system, leading to heart disorders: high blood pressure, left ventricular hypertrophy and coronary illness. Identifying the association of psychological risk factors, patients fitting in a model of psychosomatic dominant personality traits, where the main risk factors are represented by inflexibility, guilt and self-accusation feelings, associated with increase of biological indicators (proinflammatory factors, endothelial dysfunction and cytokine aggressiveness) and neuroimaging indicators (frontal, temporal, hippocampal atrophy, ventriculomegaly, cerebellum atrophy). Changes identified post-mortem in the arterioles from the frontal cortex were found also in the coronary vessels, suggesting a symmetric evolution The highlighted personality factors are responsible for the decrease of adherence and compliance both in the psychiatric and the cardiologic treatment, the patient being exposed to behavioral risks regarding life style and nutrition, factors that increase the risk for acute coronary accident. The psycho-neurobiological inspired theoretical models argument the importance of a differentiated and customized approach of the patients with depressive disorder and suicidal ideation, and they can be the base for initiating strategies for prevention of unfavorable evolution and risk of death by MI.

Corresponding author: Ileana Marinescu, Lecturer, MD, PhD; e-mail:

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5. State of the art regarding anticoagulant and thrombolytic therapy in dental procedures

Adela Cristina Lazar, Aranka Ilea, Bianca Moldovan, Anca Ionel, Andreea Simona Pop, Mariana Pacurar, Radu Septimiu Campian

Patients with anticoagulant therapy have a high thromboembolic risk. Due to the rich oro-maxillofacial vasculature and the fact that some dental procedures may cause a bleeding, the physician should be able to correlate this risk with the hemorrhagic risk. Dental procedures are a trigger for psychic stress. One of the most important changes in acute stress is in cardiovascular system. In healthy patients, these changes are reversible and have no significant consequences, but in patients with cardiovascular diseases, the response to the catecholamine stress can cause organic lesions resulting in an acute myocardial infarction or stroke. This review explores in a concise manner the biochemical changes concerning anticoagulation and thrombolytic treatment in dental procedures.

Corresponding author: Adela Cristina Lazar, Assistant Professor, DMD, PhD; e-mail:

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6. Acupuncture and the retrospect of its modern research

Feng Ifrim Chen, Andreea-Daniela Antochi, Adrian Gheorghe Barbilian

Acupuncture is one of the oldest medical practices of Traditional Chinese Medicine (TCM). This method of treatment was discovered when primitive Chinese people discovered that pain in one part of the body can be alleviated if it stings in a particular area of the body. Acupuncture has achieved to a climax in Ming Dynasty (1368-1644 A.D.), when many famous doctors specialized in this field emerged with a lot of exclusive books on acupuncture, but the most important one was Compendium of Acupuncture and Moxibustion by Yang Jizhou, which represented a new milestone in the history of acupuncture s evolution. Yang Jizhou compiled a book that presents a complete and laborious description of the meridians, collaterals, acupuncture points, manipulating methods of acupuncture and their indications. According to the ancient description of the meridians and collaterals and the research on the anatomy of Western medicine, some scholars think the meridians and collaterals are closely related to the blood vessels. In recent years, many reports have showed that acupuncture has remarkable effect on the pituitary gland and adrenal cortex system, the sympathetic nerve and adrenal medulla system, the pituitary gland and thyroid gland system, the sexual glands, and the posterior pituitary system. Thus, some researchers put forth the theory of the meridians and collaterals associated with regulatory function of the neurohumoral system, and the action of acupuncture and moxibustion is brought about by the way of the nerves and body fluid.

Corresponding author: Feng Ifrim Chen, Associate Professor, MD, PhD; e-mail:

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7. Triple immunohistochemistry for assessing the inflammatory, vascular and progression of adenomyosis

Anca-Maria Istrate-Ofiteru, Iulia-Cristina Pirvan, Daniel Pirici, Gabriela-Camelia Rosu, Mihaela Niculescu, Sabina Berceanu, Maria Magdalena Manolea, Maria Victoria Comanescu, Nicoleta-Loredana Voicu, Larisa Iovan, Mihaela Mariana Vasile, Razvan Grigoras Capitanescu, Damian Ditescu, Laurentiu Mogoanta, Costin Berceanu

Adenomyosis is a benign pathology, common to both women at reproductive age as well as later during menopause. This condition is accompanied by a strong symptomatology, which has induced intense research on this topic. From a morphological point of view, it is represented by the existence of endometrial glands and, sometimes, of the periglandular stroma (endometriosis) in the structure of the myometrium, at a significant distance from the normal endometrium. Various inflammatory, vascular and mechanical factors accentuate the symptoms and evolution of this pathology. Our study included a total number of 32 patients, eight cases for each of the following histopathological subtypes: endometrium - proliferative phase, endometrium - secretory phase, myometrium with endometrial glands (adenomyosis), and myometrium with hyperplastic transformation of endometrial glands (hyperplastic adenomyosis), respectively. We have conducted clinical, morphological and morphopathological studies of the structures in question. Using the classical histological technique (Hematoxylin-Eosin), we identified the glandular structures; utilizing immunohistochemistry, we have labeled the endometrial epithelium with the anti-cytokeratin 7 (CK7) antibody and we analyzed the periglandular cell types of the immune system: T-lymphocytes using anti-cluster of differentiation (CD) 3 antibody, macrophages using anti-CD68 antibody, mast cells using anti-tryptase antibody, periglandular vascularization with the reaction using anti-CD34/anti-CD31 antibodies, thus demonstrating their involvement in the development of adenomyosis. The interesting aspect of this study is the technique of simultaneously labeling of the inflammatory, vascular and epithelial elements.

Corresponding author: Laurentiu Mogoanta, Professor, MD, PhD; e-mail:

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8. EpCAM (MOC-31) - immunohistochemical profile and clinico-pathological correlations in different histological variants of papillary thyroid carcinoma

Elena Corina Andriescu, Simona Eliza Giusca, Delia Gabriela Ciobanu Apostol, Ludmila Lozneanu, Irina-Draga Caruntu

EpCAM is a cell-adhesion molecule, located at the basolateral membrane of the normal epithelial cells. Changes in EpCAM expression are reported in several malignancies, as an early indicator for carcinogenesis. Our study aimed to evaluate the EpCAM expression in different subtypes of papillary thyroid carcinoma (PTC), focusing on its role in the risk stratification of the histological variants and its relationship with the classical clinico-pathological characteristics. We analyzed 70 selected cases of PTC, divided into low- and high-risk groups, according to histological criteria. Immunohistochemical (IHC) exam was performed using MOC-31 antibody, against the EpEx-MOC-31 extracellular domain of EpCAM molecule. MOC-31 expression was assessed at the membrane and cytoplasmic levels, using a semi-quantitative score that allowed the classification in low- and high-score category, respectively. The relationship between MOC-31 expression and clinico-pathological characteristics was statistically evaluated. We found statistically significant correlation between MOC-31 expression (low versus high) and the risk groups, tumor size and tumor relapse. The twofold analysis, based on score system and risk category, showed an association between low score and low risk in 80% of all cases, low score and high risk in 56% of the cases, high score and low risk in 36% of the cases and high score and high risk in 44% of the cases. The modification of MOC-31 location, with consequent changes in its interactions with other cell-adhesion molecules, is integrated in the carcinogenic mechanism. Our study demonstrates the large variability of MOC-31 expression in PTC histological variants, and highlights the differences between the low and high MOC-31 expression that could work as a useful tool for the identification of those high-risk PTC cases, with unfavorable clinical outcome.

Corresponding author: Ludmila Lozneanu, MD, PhD; e-mail:

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

Gergo Raduly, Zsuzsanna Pap, Lorand Denes, Annamaria Szanto, Tamas-Csaba Sipos, Zoltan Pavai

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 Targu 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.

Corresponding author: Zsuzsanna Pap, Associate Professor, MD, PhD; e-mail:

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10. Clinical-pathological correlations in Warthin tumors of parotid gland: a series of 10 cases

Anca Sava, Alexandru Nemtoi, Cristinel Ionel Stan, Gabriela Florenta Dumitrescu, Danisia Haba, Cristian Constantin Budacu, Vlad Covrig, Victor Vlad Costan, Lucian Eva

Warthin tumor is described using various terms, such as papillary cystadenoma lymphomatosum, adenolymphoma or monomorphic adenoma. It is a medical condition related to the salivary glands, namely a benign cystic tumor which contains an epithelial component and an abundant lymphoid stroma. It is also named Warthin tumor after Aldred Scott Warthin, the pathologist who described this entity in 1929 by observing it in two patients. Warthin tumor is a benign one and ranks secondly in terms of the most common not malignant salivary gland tumor located in the parotid gland. Because of its cystic nature, from the clinical point of view, it appears to be a slow-growing tumor often fluctuant on palpation. In terms of the treatment of choice, complete excision with wide tumor-free margins is preferred. The aim of the present article is to evaluate possible correlations between clinical-pathological features and postoperative complications in a target group made up of 10 patients diagnosed with Warthin tumor of the parotid gland admitted for surgery in a period of 21 years and to compare the results with literature.

Corresponding author: Alexandru Nemtoi, Assistant, MD, DMD, PhD; e-mail:; Cristinel Ionel Stan, Associate Professor, MD, PhD; e-mail:

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11. Behavior pattern of early-stage ocular surface squamous cell carcinoma in non-HIV patients

Alin-Stefan Stefanescu-Dima, Maria-Rodica Manescu, Andrei-Theodor Balasoiu, Maria Balasoiu, Carmen-Luminita Mocanu, Horia-Tudor Stanca, Maria Filoftea Mercut Nicolcescu

Ocular surface squamous neoplasia (OSSN) is a malignant or dysplastic lesion that has its origins in the epithelial cells at the ocular surface. The structures from which these lesions can arise are the conjunctiva, the limbus, and the cornea. Our study was conducted on a group of seven patients with ocular surface squamous cell carcinoma (SCC). Histopathologically diagnosed SCCs were then assessed as well, moderately and poorly differentiated, depending on which area of differentiation dominated in Hematoxylin-Eosin staining. For the immunohistochemical analysis, the following antibodies (markers) were used: Ki67, p53 and B-cell lymphoma 2 (Bcl-2), E-cadherin, and vascular endothelial growth factor (VEGF). Our study group was composed of seven cases of SCCs of the ocular surface. Three were below in T1 American Joint Committee on Cancer (AJCC) stage, two cases were in T2 AJCC stage, and two cases were in T3 AJCC stage. None of our cases were T4, N1 or M1 AJCC tumors. Four of the cases were histopathologically moderately differentiated SCCs of the ocular surface and three were poorly differentiated SCCs. None of the seven patients present human immunodeficiency virus (HIV) infection. P53 immunostaining was strongly present in our study. Bcl-2 overexpression is not a fact that our study highlights. The expression of Ki67 proliferation marker was low in our study. Our study on ocular surface SCC reveals negative assessment of VEGF immunostaining. E-cadherin expression in our study was positive. Ocular surface SCCs are slow growing tumors, with very low metastasis potential, when HIV-infection is not present.

Corresponding author: Andrei-Theodor Balasoiu, Assistant Professor, MD, PhD; e-mail:

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12. Immunoexpression of Snail, Twist1 and Slug in clear cell renal cell carcinoma

Bianca Catalina Andreiana, Alex Emilian Stepan, Oana Taisescu, Anne-Marie Al Khatib, Mirela Marinela Florescu, Cristiana Eugenia Simionescu, Anda-Elena Crisan

Clear cell renal cell carcinomas (ccRCC) represent about 80% of the malignant neoplasia with this localization. Snail, Twist1 and Slug are transcription factors and play a central role in the epithelial-mesenchymal transition (EMT), which is involved in the progression of renal cell carcinoma (RCC). In this study, we analyzed the immunoexpression of these transcription factors in 50 cases of ccRCC, in relation to histopathological aggressiveness parameters of the lesions. The results indicated the association of Snail and Twist1 expression with high Fuhrman grade, as well as the association of Slug expression with low Fuhrman grade. The immunoexpression of Snail and Twist1 was significantly superior for advanced stages and Slug was overexpressed in early stages of ccRCC. Our study supports the usefulness of the Snail, Twist1 and Slug expression for the appreciation of aggressiveness in ccRCC, the panel being attractive for targeted therapy.

Corresponding author: Cristiana Eugenia Simionescu, Professor, MD, PhD; e-mail:; Alex Emilian Stepan, Associate Professor, MD, PhD; e-mail:

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13. Modern interdisciplinary monitoring of cervical cancer risk

Mihaela Badea, Alexandru Baros, Roxana Elena Bohiltea, Irina Ecaterina Julea, Florentina Ligia Furtunescu, Anca-Maria Istrate-Ofiteru, Larisa Iovan, Monica Mihaela Cirstoiu, Miruna Ruxandra Burcin, Natalia Turcan, Adrian Neacsu, Costin Berceanu

Currently, Romania ranks first in Europe with regard to cervical cancer mortality. A new solution proposed for optimizing cytology-based screening, before seeing the risk associated with minor abnormalities results, is the use of molecular markers. This study concerns atypical squamous of undetermined significance (ASC-US) results, the grey zone of cytology that hides up to 15% high-grade lesions, to see how dual immunocytochemistry (ICC) staining for p16INK4a/Ki67 help to better identify and manage high-risk (HR) ASC-US patients. We included and reviewed 183 cases with ASC-US results and p16INK4a/Ki67 double staining (DS) performed in MICOMI Clinic (Bucharest) during 2014-2016. All patients were referred for colposcopy and biopsy if appreciated as necessary and followed-up at six and 12 months. One DS(+)/HR human papillomavirus (HPV) negative case was positive for HPV73 Group IIB International Agency for Research on Cancer (IARC). The mean age for ASC-US in our study group was 32 years, with a median of 31 years and 31% of patients were aged 25-29 years. The sensibility of p16INK4a/Ki67 double immunostaining was 100%, the specificity 88%, the positive predictive value (PPV) was 82%, and the negative predictive value (NPV) was 100%. The use of p16INK4a/Ki67 ICC test optimizes the medical approach towards screening or monitoring especially in ASC-US HR HPV(+) young patients, unnecessary colposcopies are avoided thus invasive gestures at nulliparous are limited.

Corresponding author: Roxana Elena Bohiltea, Lecturer, MD, PhD; e-mail:; Alexandru Baros, Assistant Professor, MD, PhD; e-mail:

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14. Thymoquinone reverses nonalcoholic fatty liver disease (NAFLD) associated with experimental hypothyroidism

Nasra Naeim Ayuob, Ahmed Abdel-Hamid Mohamed Abdel-Hamid, Ghada Mohamed Moneir Helal, Wafaa Alaa Mubarak

Objectives: To assess the efficacy of thymoquinone (TQ), the most active constituent in Nigella sativa, which is a medicinal plant from the Ranunculaceae family, in restoring the normal liver structure after 6-propyl-2-thiouracil (PTU)-induced hypothyroidism and explore the mechanism behind this. Materials and Methods: Hypothyroidism was induced in rats by injection of PTU [6 mg/kg body weight (b.w.)] for six weeks. Twenty-four adult male Wistar rats were divided into four groups; the control, TQ-treated at the dose 400 mg/kg b.w., untreated hypothyroidism and TQ-treated hypothyroid groups. Serum levels of thyroid hormones and antioxidant profile were measured. Real-time polymerase chain reaction was used to assess gene expression of catalase (CAT). Liver was histopathologically examined using routine and immunohistochemical techniques. Results: Livers of rats with hypothyroidism displayed nonalcoholic fatty liver disease (NAFLD) in the form of steatosis as well as nonalcoholic steatohepatitis (NASH). Moreover, there was an intralobular inflammatory reaction associated with significant (p<0.05) increases in the density of resident hepatic macrophages [cluster of differentiation 68 (CD68)+ cells], as well as in activated hepatic stellate cells, alpha-smooth muscle actin (alpha-SMA) index in livers with hypothyroidism. Resolution of hypothyroid NAFLD was observed in livers after treatment with TQ. The significantly increased (p<0.05) steatosis, lobular inflammation, NAFLD activity scores, alpha-SMA index as well as CD68+ cells induced by hypothyroidism were corrected after TQ administration. Up-regulation of the CAT gene in livers with hypothyroidism after treatment with TQ supported our hypothesis of its antioxidant mechanistic hepatoprotective action. Conclusions: TQ efficiently restores the normal liver histology in hypothyroid rats with up-regulation of the antioxidant CAT gene.

Corresponding author: Nasra Naeim Ayoub, MD, PhD;,

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15. Hypertensive cardiomyopathy - histopathological and immunohistochemical aspects

Anda-Mariana Brasoveanu, Laurentiu Mogoanta, Gheorghe Dan Malaescu, Octavian Ion Predescu, Bogdan-Virgil Cotoi, Feng Ifrim Chen

Arterial hypertension (AH) represents the main cause of morbidity and mortality all over the world. Approximately 40% of the adults aged over 25 years old and about 90% of the persons aged over 80 years old suffer from AH. It is a multifactorial condition, in whose etiopathogeny there are involved numerous genetic, metabolic and environment factors. In its turn, AH is one of the most important risk factors for heart disease, stroke, heart failure, kidney disease and peripheral vascular diseases. In hypertensive patients, it progresses into the left ventricle hypertrophy, as a result of some major changes of the cardiomyocytes, but also of the extracellular conjunctive matrix (ECM). We evaluated some histopathological and immunohistochemical changes induced by AH on some fragments of myocardium from the left ventricle. There was observed an increase of the ECM quantity, manifested by the expansion of the intercellular spaces, fibrillar collagen synthesis and its deposit in the perivascular and interstitial spaces, a significant reduction of the number of microvessels in the myocardium, the alteration of cardiomyocyte structure, by reducing the quantity of desmin and of the intercellular connections, by reducing cluster of differentiation 56 (CD56) (neural cell adhesion molecule 1 - NCAM1) immunomarker.

Corresponding author: Laurentiu Mogoanta, Professor, MD, PhD; e-mail:

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16. Role of imagistic techniques in diagnosing soft-tissue vascular anomalies in pediatric population - a 5-year experience

Simona Cerbu, Teodora Smaranda Arghirescu, Maria Corina Stanciulescu, Cristian-Eugen Timofte, Elisa Mussuto, Elena Rodica Heredea, Ioana Delia Horhat, Emil Radu Iacob, Florin Birsasteanu, Eugen Sorin Boia

Soft-tissue vascular anomalies have a worldwide estimated prevalence of 4.5% in the pediatric population. From January 1, 2014 until December 31, 2018, imagistic and histological evaluations were performed in 214 patients aged between one day and 18 years old, who were diagnosed with different soft-tissue vascular anomalies in our Center. From the 214 patients included in the study, 36.45% (n=78) were males, 63.55% (n=136) were females and 37.38% (n=80) of the patients were less than one year of age at time of admission. Infantile hemangioma was the most frequent type of soft-tissue vascular anomaly (35.51%) and the face was the most frequent affected region (25.7%). Ultrasound (US) examination is the most used imaging technique due to its wide accessibility and for providing valuable information about the anatomical localization of the lesions, the type of vessels involved, distribution and density of vascularization. Magnetic resonance imaging (MRI) can be used for assessing the extent of deep or large lesions, but it usually requires anesthesia. Computed tomography (CT) is useful when patients present contraindications to anesthesia and it has the advantage of a shorter image acquisition time. Histological studies have an important role in establishing the diagnosis even for the atypical cases of soft-tissue vascular anomalies. Furthermore, the prognosis depends on the histological type. In conclusion, there is a need for collaboration between the clinician, radiologist, pathologist and surgeon in order to establish a precise diagnosis and therapeutic strategy for each patient.

Corresponding author: Emil Radu Iacob, Lecturer, MD, PhD; e-mail:,; Ioana Delia Horhat, Assistant Professor, MD, PhD; e-mail:

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17. The study of tumor architecture components in prostate adenocarcinoma using fractal dimension analysis

Razvan Mihail Plesea, Mircea-Sebastian Serbanescu, Dragos Viorel Ciovica, Gabriela-Camelia Rosu, Valentin Tiberiu Moldovan, Raluca Maria Bungardean, Nirvana Alina Popescu, Iancu Emil Plesea

Aim: The aim of the study is to evaluate the three main components of the tumor architecture in correlation with two different grading systems of prostate adenocarcinoma (PA) using the fractal dimension (FD) analysis. Patients, Materials and Methods: 433 fields with different patterns of PA selected from 83 patients with total prostatectomy according to Gleason and Srigley grading systems were selected. Four serial sections were cut and stained in order to assess the following parameters: tumor grading with Hematoxylin-Eosin (H-E), tumor cells architecture (GO) with Gomori technique, tumor stroma architecture (TC) with Goldner s trichrome, and vascular network (VN) architecture with cluster of differentiation 34 (CD34) immunomarker. Images were binarized with variable user-defined empiric threshold for Goldner s trichrome staining and CD34 immunostaining and k-nearest neighbor approach for GO staining. The FD was computed for each binary image using a box-counting algorithm. The three computed values were used for clustering and classification, k-nearest neighbor proving to be a good choice with a classification rate, due to the irregular distribution of cases in different patterns. Values tending to 1 had the meaning of a more Linear type distribution and values tending to 2 had the meaning of a more Area type distribution. Results: Tumor cells architecture had a more ordered smooth ascending trend towards area-like type of distribution (with FD>1.5) in Srigley system than in Gleason system. Tumor stroma architecture had almost the same type of distribution - between linear-like and area-like (FD cca. 1.5) - in both grading systems. VN architecture had a more linear-like type of distribution (FD<1.5), with a descending trend towards high-grade patterns in both systems. Tumor cells architecture had a direct correlation with tumor stroma architecture and VN architecture (p-value of Pearson s test <0.001), while tumor stroma architecture and VN architecture proved no correlation (p-value of Pearson s test >0.05), irrespective of grading pattern. Conclusions: Tumor cell population is remodeling and adapting TC and VN in the same way its architectural disposal evolves. TC and VN develop independently of each other, the former towards Area type and the latter towards Linear type of architectural disposal as the degree of differentiation is decreasing. FD analysis proved that Srigley system is more accurate in grading PA than Gleason system.

Corresponding author: Mircea-Sebastian Serbanescu, Lecturer, MD, PhD; e-mail:

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18. Squamous cell carcinoma of the penis: a clinicopathological study from a population with late circumcision

Dilek Ertoy Baydar, Hampar Akkaya, Duygu Dusmez Apa, Nebil Bal, Asli Demirsam, Berrin Gucluer, Nalan Nese, Aysegul Akder Sari, Sevin Kirdar, Bulent Akdogan, Erdem Karabulut

Squamous cell carcinoma (SCC) of the penis has been subject to only a few studies in populations where late childhood circumcision is performed. To asses clinicopathological features and human papillomavirus (HPV) status of penile SCC in men with late circumcision, eight institutions in the country volunteered to collaborate and 15 cases of penile SCC were collected from their pathology archives. The presence and genotype of HPV were determined in addition to clinicopathological features of the tumors. Findings were correlated with disease outcome. The mean age of the patients evaluated was 66.5 years. Histological subtypes were usual SCC (6/15), papillary (2/15), mixed (2/15), basaloid (2/15), acantholytic (1/15), pseudohyperplastic (1/15), and warty-basaloid (1/15) carcinomas. HPV was identified in 33.3% of samples; HPV16 was detected in 60% of positive cases and was associated with basaloid and/or warty morphology. Cause-specific 1-year and 2-year survivals were 76.9% and 54.5%, respectively. The usual subtype and nodal metastasis were associated with worse outcome (p=0.045 and p=0.047, respectively). As a conclusion, our results suggest an inclination for penile SCC to develop at a later age in a population with late circumcision than the patients from the regions of high penile cancer incidence. These men seem to have less frequent HPV association and their outcome appears poorer than other populations, although reaching substantial provision is not possible due to our limited case number.

Corresponding author: Dilek Ertoy Baydar, Professor, MD; e-mails:,

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19. Immunoexpression of E-cadherin, Snail and Twist in colonic adenocarcinomas

Anne-Marie Al Khatib, Claudiu Margaritescu, Oana Taisescu, Bianca Catalina Andreiana, Mirela Marinela Florescu, Raluca Niculina Ciurea

Epithelial-mesenchymal transition (EMT) is an important mechanism in tumor progression. Snail is a transcription factor, expressed in cells which have undergone almost complete EMT and have left the tumor, and Twist is considered important in the process of metastasis, both playing a major role in EMT by indirect inhibition of E-cadherin. The study analyzed the immunoexpression of E-cadherin, Snail and Twist in 46 cases of colonic carcinomas in comparison with some histopathological prognostic factors. The quantification of reactions was done by using a composite score (CS) resulted from multiplying the percentage of marked cells with the intensity of immunostaining. The majority of cases were moderately differentiated tumors, corresponded to stage III, with vascular and perineural invasion. All cases presented positive cytoplasmic and nuclear signals for Snail and Twist. The immunostaining for both markers was intense, with the highest values of CS in G2 and G3 advanced, invasive vascular colonic carcinomas, in comparison with G1, early stage lesions. We found positive significant linear correlation of Snail and Twist expression. The results obtained indicate the implication of Snail and Twist in colonic carcinoma aggressiveness, useful aspect in the oncological evaluation of patients and guided therapy.

Corresponding author: Claudiu Margaritescu, Professor, MD, PhD; e-mail:

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20. An important morphological feature of the face: upper lip length

Bianca Maria Negrutiu, Luminita Ligia Vaida, Bianca Ioana Todor, Adrian Sorin Judea, Ioana Elena Lile, Abel Emanuel Moca, Claudia Teodora Judea-Pusta

The oral cavity, including the lips, is considered one of the most important features of the face, taken into consideration when people inter-relate. Upper lip, in particular, can have a great influence on the aspect of a smile, which is why its proportional length and thickness can improve a lot a persons smile. The aim of this study was to determine the average length of the upper lip in the Caucasian population, considering age and gender. The average upper lip length determined on the lateral skull radiography was 20.25+/-2.555 mm. The average length of the upper lip was 19.79+/-1.641 mm in the age category under 12 years and 20.32+/-2.664 mm in the age category over 12 years. The average length of the upper lip was 19.95+/-2.4 mm in women and 21.18+/-2.79 mm in men. We can conclude that women have lower values, while men have higher values of the upper lip length, and that the younger the patient is, the shorter the length of the upper lip is. Moreover, the Caucasian population proved to have a shorter upper lip compared to the Asian or Negroid population.

Corresponding author: Luminita Ligia Vaida, Professor, DDS, PhD; e-mail:; Abel Emanuel Moca, Teaching Assistant, DMD, PhD Student; e-mail:

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21. Polycystic kidney disease in neonates and infants. Clinical diagnosis and histopathological correlation

Diana Stefania Mateescu, Mihaela Gheonea, Mihaela Balgradean, Augustina Cornelia Enculescu, Mircea-Sebastian Serbanescu, Florina Nechita, Daniel Pirici, Ion Rogoveanu

A significant cause of end-stage renal disease in infants (40% to 50% of cases) is represented by the group of renal cystic diseases. Actually, the fourth cause of renal failure in young adults is the autosomal dominant polycystic kidney disease (ADPKD). Moreover, the most common genetically inherited kidney disease was proved to be ADPKD, affecting 1-5 per 10 000 individuals. The study was conducted over a period of three years (July 26, 2015-October 30, 2018) on 22 patients aged between two days and 36 months, diagnosed with polycystic kidneys that presented multiple hospital admissions in the Department of Nephrology, Maria Sk?odowska Curie Emergency Children s Hospital, Bucharest, Romania. The nephrectomy sections were obtained from the material of the Department of Pathology of the same Hospital. Prenatal ultrasonography results were correlated with positive family history of polycystic kidney disease (PKD), fetal enlarged kidneys and oligohydramnios. Neonatal diagnosis of PKD was considered when some of the neonates presented palpable flank masses that caused fetal dystocia. On the other hand, the pediatric clinical examination of older infants revealed abdominal distention secondary to renal masses. After surgical resection, the overall aspect of the kidneys showed that the normal parenchyma had been mostly replaced by cysts with thin, translucent walls that contained a clear fluid. Microscopy confirmed that the parenchyma was mostly replaced by dilated cysts delineated by simple cuboidal or simple flattened epithelium, with areas of remnant fetal kidney parenchyma separated by an enriched stroma. Immunohistochemistry for blood vessels (CD34) revealed normal fine walled blood vessel arcades in the control kidneys, while in most areas from polycystic disease, the blood vessels exhibited enlarged, thickened endothelium, and less collapsed lumens. Regarding the proliferative capacity of the tissues, our Ki67 immunostaining revealed that the less formed, younger tubules in the pathological state had a higher proliferative index compared to control tissue. There seemed to be less albumin immunostaining in the epithelia of the distal contort tubules but that distinction was present also in our pathology. The overall expression level was reduced in polycystic cases (p<0.05), and it could be that this expression decrease might be related to the reduced function of these kidneys. According to what literature states, we have emphasized in our study that aquaporin 1 (AQP1) showed overall decreased reactivity in PKD along with its expression in proximal tubule epithelia.

Corresponding author: Daniel Pirici, Professor, MD, PhD; e-mail:

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22. The clinical-morphological profile of tuberculous pleurisies - our experience in relation to literature data

Dragos Nicolosu, Iancu Emil Plesea, Alin Dragos Demetrian, Razvan Mihail Plesea, Elena Leocadia Popescu, Irina Ruxandra Strambu, Tiberiu Tataru

Aim: The authors made a morphological evaluation of pleural tissue fragments from patients hospitalized in Thoracic Surgery Department of the Emergency County Hospital of Craiova, Romania, over a period of 26 years, diagnosed with tuberculous lesions in the Pathology Department of the same Hospital. Patients, Materials and Methods: The studied material consisted of pleural tissue samples taken by biopsy or surgical excision from 39 cases coming out of 841 patients investigated in the above-mentioned period of time and diagnosed from histological point of view with tuberculosis (TB). Granuloma cell population was assessed using immunohistochemical method. For diagnostic confirmation, Ziehl-Neelsen staining has been used as a rule but, in some cases, immunohistochemistry was also used. Results: TB lesions predominated in men usually around or over 50 years old. The diagnostic was suspected in almost half of the cases. Right cavity was more affected and the extended fibrosis was present in a significant number of cases. The inflammatory conflict was of reactive type, with giant Langhans cells granulomas and acidophilic necrosis but sometimes with superinfection or significant fibrous sequelae. Conclusions: Pleural effusions of TB origin are a reality more and more present due to the recrudescence of pulmonary TB in the last decades. Their presence should be suspected if faced to a unilateral pleural effusion with free-flowing fluid occurred almost often to a man of any age from youth to elderly.

Corresponding author: Iancu Emil Plesea, Professor, MD, PhD; e-mail:

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23. Are there any correlations between demographic characteristics, tumor location, and Ki-67 labeling index in intracranial atypical meningiomas (WHO grade II)?

Andrei Ionut Cucu, Claudia Florida Costea, Mihaela Dana Turliuc, Gabriela Florenta Dumitrescu, Anca Sava, Ion Poeata

Background/Aim: Atypical meningiomas (AMs) account for about 30% of all meningiomas and it is difficult to predict their behavior. Nevertheless, the identification of protein markers responsible for the regulation of cell proliferation can be helpful. The purpose of this study is to find possible correlations between demographical characteristics of patients with AMs, tumor anatomic location, and intratumoral immunohistochemical (IHC) expression of Ki-67 labeling index (LI). Patients, Materials and Methods: We carried out a retrospective review of 29 patients with intracranial AMs [World Health Organization (WHO) grade II] who underwent resection of AMs at Professor Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania, between January 1, 2014 and December 31, 2016. We searched for their demographic characteristics (age and gender) and tumor location from patients medical files. The histological slides were reviewed in order to assess the Ki-67 LI. Results: Out of the 29 patients analyzed, 51.72% were females having AMs, with a mean Ki-67 LI of 8.6%, and 48.27% were males with AMs, revealing a mean Ki-67 LI of 8.5%. Considering tumor anatomic location, 82.75% were non-skull base AMs (presenting a mean Ki-67 LI of 8.9%) and 17.24% were skull base AMs (showing a mean Ki-67 LI of 8.2%). Although we did not find any statistically significant correlation between gender, age, tumor anatomic localization, and Ki-67 expression, our study revealed that the mean Ki-67 LI for AMs was 8.7% (ranging from 6% to 15%) and was close to values obtained by other authors. In terms of gender distribution, we have noticed that AMs diagnosed in male patients had a mean Ki-67 LI almost equal to that in female patients even though some studies found Ki-67/MIB-1 LIs significantly higher in male patients than in female patients. Also, we did not find any significant correlation between Ki-67 LI and tumor anatomic location as reported by other studies. Conclusions: Despite the fact that statistically we could not find any significant correlation regarding patients gender and age, tumor anatomic location, and Ki-67 LI expressed by AMs, IHC detection of Ki-67 antigen remains an important tool in addition to routine histological evaluation, which can be used to predict tumor behavior of meningiomas.

Corresponding author: Claudia Florida Costea, Senior Lecturer, MD, PhD; e-mail:; Mihaela Dana Turliuc, Associate Professor, MD, PhD; e-mail:

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24. Immunoexpression of E-cadherin, P-cadherin and fibronectin in gastric carcinomas

Maria Dobritoiu, Alex Emilian Stepan, Claudiu Margaritescu, Cristiana Eugenia Simionescu, Cristin Constantin Vere, Michael Schenker, Anda-Elena Crisan

One of the mechanisms involved in gastric carcinomas progression is represented by epithelial-mesenchymal transition (EMT), a complex process during which tumor cells acquire an invasive and migratory mesenchymal phenotype. In this study, we analyzed the immunoexpression of E-cadherin, P-cadherin and fibronectin in 50 gastric carcinomas, in relation with the tumoral type, differentiation grade and lesions stage. The reactions presented variable patterns related to lesions stage. Membrane and cytoplasmic reactions were present in 62% of cases for E-cadherin and in 56% of cases for P-cadherin, being present only cytoplasmic in 34% of cases for fibronectin. The immunoexpression for E-cadherin and P-cadherin was superior in tubular gastric carcinomas, of low grade and early stage, while fibronectin expression was superior in discohesive or mixed gastric carcinomas, of high grade and in advanced stages. Negative E-/P-cadherin and positive fibronectin immunophenotype may be associated with aggressive gastric carcinomas and supports the EMT involvement in gastric carcinogenesis.

Corresponding author: Cristiana Eugenia Simionescu, Professor, MD, PhD; e-mail:; Alex Emilian Stepan, Associate Professor, MD, PhD; e-mail:

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25. Histological aspects of full-thickness skin grafts augmented with platelet-rich fibrin in rat model

Oliviu Nica, Dragos George Popa, Alexandru Florian Grecu, Eduard Mihai Ciuca, Marius Eugen Ciurea

Background and Objectives: The restoration of the damaged tissue commences very early with a regulated sequence of biochemical events set into motion to repair the damage. While the understanding of this entire process is still incomplete, it has been established that platelets play a decisive role not only in hemostasis, but also in the wound healing process, through an abundance of growth factors and other signaling cytokines modulating the inflammatory response. To this end, we attempted to evaluate the effect of a platelet-rich biomaterial - platelet-rich fibrin (PRF) - in the augmentation of full-thickness skin grafts (FTSGs). Materials and Methods: Skin defects were performed on the rats dorsum and covered with FTSGs. The test group wound bed was treated with PRF before the suture of the graft. Skin graft specimens were obtained from the control and test group rats for histological and immunohistochemical examination on the 21st postsurgical day. Our study included 40 male Wistar rats. Average thickness of epidermal cell layers was recorded for each wound site. The average fibroblast count was compared between the control and test (PRF-augmented FTSG) groups. Blood vessel count and vascular density - the blood vessels were identified under low-power microscopy. The prominent vascular areas were then scanned in higher-power fields; individual vessels were marked and counted by hand. Vascular density was calculated. Mean vascular count for each graft was then calculated. Results: The mean thickness of the epidermal layer was significantly higher and closer to the physiological epidermal thickness, in the test group than in the control group. The average fibroblast and fibrocyte count in the dermal layer in FTSGs augmented with PRF was higher than in the control group. We discovered a statistically insignificant increase in the blood vessel count and vascular density of the test group, compared to the control group. Conclusions: Our limited data supports the theory that the addition of PRF to FTSG recipient wound beds has the potential to improve graft take and regulate the proliferation of a thicker and more uniform epidermis, while decreasing healing time and dermal necrosis rates.

Corresponding author: Alexandru Florian Grecu, MD, PhD Student; e-mail:

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26. Histopathological elements analyzed in dynamics in mechanical bowel obstructions - experimental study on laboratory animals

Ionut Simion Coman, Costin George Florea, Daniel Gheorghita, Cristin Coman, Angelica-Iulica Dinu, Elena-Violeta Coman, Vlad Andrei Porojan, Oana-Ilona David, Stefan Iulian Bedereag, Roxana Corina Sfetea, Sabina Gabriela Ciuvica-Tanasescu, Gabriel Petre Gorecki, Valentin Titus Grigorean, Mircea Beuran

Bowel obstruction is a syndrome that produces important alterations to the digestive tract, both macroscopically and microscopically. We conducted an experimental study using rats, Wistar strain, as subjects, dividing them into three groups. The group A consisted of six rats and served as control group, in the first day of the experiment a surgical procedure being performed to resect a small bowel and a colic segment to be analyzed microscopically afterwards. The 10 subjects from group B underwent a surgical procedure, in which we induced a mechanical bowel obstruction in the sigmoid colon, while to the 10 subjects from group C we induced a mechanical bowel obstruction in the small bowel. The initial protocol implied to observe the macroscopic modifications from five subjects from each group B and C after two days and afterwards to resect the digestive tract segment adjacent to the obstruction site. After another two days, a similar procedure was planned for the remaining subjects alive from both groups. A few subjects from group C died prematurely and the initial protocol had to be partially modified. The results highlighted an important distension of the digestive tract proximal to the obstruction, with important microscopically reactions, including edema, thrombosis, ischemic lesions and accumulation of polymorphonuclear neutrophils (PMN) and macrophages.

Corresponding author: Valentin Titus Grigorean, Professor, MD, PhD; e-mail:

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27. Correlations between infection patterns and eye damage in reactive arthritis

Simona Banicioiu-Covei, Ananu Florentin Vreju, Paulina Lucia Ciurea

The purpose of the study was to correlate the infectious patterns (urogenital, enteral) with ocular manifestations, such as conjunctivitis or acute anterior uveitis in reactive arthritis (ReA). The transversal, observational study was conducted in the Clinic of Rheumatology, University of Medicine and Pharmacy of Craiova, Romania, during the period 2012-2015, and included 112 patients. They were divided into three groups, as follows: Group I (52 ReA cases), Group II (30 other spondyloarthritis cases), Group III (40 osteoarthritis cases). Ophthalmologic screening was performed, together with the detection of human leukocyte antigen B27 (HLA-B27) and the infectious trigger. Within Group I, 42 (80.76%) patients presented genitourinary infections (78.57% Chlamydia trachomatis, 21.43% Ureaplasma urealyticum), 10 (19.23%) patients presented enteral infections (Yersinia enterocolitica and Salmonella). Compared with the other two groups, the patients from the first group were documented with more conjunctivitis episodes. Although anterior uveitis is more common in ankylosing spondylitis (AS), in the present study more cases were identified in Group I (11.9%) than in Group II (6.67%) and no case were recorded in Group III. Most of patients from Group I were HLA-B27 positive. The etiologic profile of ocular manifestations in ReA is dominated by genitourinary infections - C. trachomatis and U. urealyticum, respectively. Cases of recurring uveitis are associated with elevated levels of anti-immunoglobulin A (IgA).

Corresponding author: Simona Banicioiu-Covei, Assistant Professor, MD; e-mail:

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28. Correction of Class III malocclusions through morphological changes of the maxilla using the protraction face mask by three different therapeutic approaches

Luminita Ligia Vaida, Abel Emanuel Moca, Bianca Maria Negrutiu, Alexandru Iosif Precup, Bogdan Andrei Bumbu, Ioana Scrobota, Simion Bran

Face mask (FM) therapy used for maxillary protraction improves the facial profile in patients with Class III malocclusion. The aim of this study was to compare the sagittal morphological changes of the maxilla through three different therapeutic approaches, respectively using removable appliances (RA), rapid maxillary expansion (RME) and surgically assisted rapid maxillary expansion (SARME), each of them in combination with the FM therapy in growing and non-growing patients. The sample, consisting of 42 orthodontic patients aged 7-21, was divided into four groups, according to their age. The first group of patients, aged 6-9 (RA + FM group), received treatment with RA in combination with FM, the second group of patients, aged 10-13 (RME + FM pubertal group), received treatment with RME in combination with FM, the third group of patients, aged 14-16 (RME + FM postpubertal group), received treatment with RME and FM, and the fourth group of patients, aged 17-21 (SARME + FM group), underwent SARME in combination with FM. To assess the sagittal skeletal changes of the maxilla, the sella-nasion-A point (SNA) and A point-nasion-B point (ANB) angles were measured at the beginning and after the FM therapy. The differences in the evolution of the SNA angle between the groups were statistically significant (p<0.001). Post-hoc analysis showed that patients aged 6-9 had the highest evolution, statistically higher than patients aged 14-16 (p=0.007) or patients aged 17-21 (p<0.001). The evolution of the SNA angle was significantly higher in patients aged 10-13, in comparison to patients aged 17-21 (p<0.001). The efficiency of the FM therapy alone or associated with RME depends on patients growing period. In non-growing patients, the FM therapy is efficient when associated with SARME.

Corresponding author: Abel Emanuel Moca, Teaching Assistant, DMD, PhD; e-mail:; Alexandru Iosif Precup, Teaching Assistant, DMD, PhD; e-mail:

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29. Structure-grain size-synthesis route of silver nanoparticles: a correlation with the cytotoxic effect

Otilia-Ruxandra Vasile, Ecaterina Andronescu, Roxana Trusca, Eugeniu Vasile, Alina-Maria Holban, Mariana-Carmen Chifiriuc, Florin Iordache, Horia Maniu, Coralia Bleotu, Ionela Andreea Neacsu, Bogdan-Stefan Vasile

Although engineered silver (Ag) nanopowders offer great promise in various fields of biomedical, industrial and ecological applications, insufficient data is known about their cytotoxicity. The purpose of the present study was the synthesis and then the determination of cytotoxicity effect of Ag powders using the pyrosol method, at various temperatures of 600 degrees C, 650 degrees C and 700 degrees C, respectively by sol-gel method and heat treatments at 500 degrees C, 600 degrees C, 700 degrees C and 800 degrees C. From the structural, compositional and morphological point of view, Ag samples were characterized by using X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) coupled with selected area electron diffraction (SAED) techniques. There is an influence of the synthesis route on Ag particles, which is shown as their cytotoxicity, different sizes of micro and nanosilver synthesized powders, which were evaluated in comparison depending on the work methods. Their cytotoxicity was evaluated based on their influence on cellular morphology and proliferation rate, cell cycle and apoptosis of undifferential stem cells, endothelial cells and tumoral cells, assessed through flow cytometry, cloning and MTT assay. The results showed that the cytotoxicity of the obtained Ag nanoparticles (NPs) depends on the synthesis route, the pyrosol synthesized NPs exhibiting a higher cytotoxicity as compared to those obtained by the sol-gel method.

Corresponding author: Bogdan Stefan Vasile, Scientific Researcher III, PhD Eng; e-mails:,

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30. Morphometric characteristics of fibrocartilaginous tissue in the herniated intervertebral disc

Ahmed Abu-Awwad, Roxana Folescu, Daniel Laurentiu Pop, Andrei Gheorghe Marius Motoc, Dumitru Manuel Oprea, Mariana Tudoran, Carmen Lacramioara Zamfir, Cosmin Ioan Faur, Dinu Vermesan, Bogdan Nicolae Deleanu, Bogdan Corneliu Andor, Horia George Haragus

The purpose of this research was to identify a possible correlation between the morphometric characteristics of fibrocartilaginous tissue in the intervertebral herniated disc fragment and the clinical and imagistic characteristics of patients with back pain. Sixty-two samples were included in this study. Intervertebral herniated disc fragments obtained during surgery (microdiscectomy) were analyzed histologically and morphologically. The analyzed fragment tissues from herniated lumbar discs were from L3-L4, L4-L5 or L5-S1 levels. The average number of chondrons encountered in a visual field was 35 (ranging from 8 to 51). The minimum chondrons surface area - 493.4 pixels(2) [from 188 to 925 pixels(2)] and the average peak area of chondrons - 5250.9 pixels(2) ranging from 1171 to 11811 pixels(2)] and the median was 785.4 pixels(2) [values between 247.5 and 1621 pixels(2)]. With age control, a correlation between the average chondron area and the Pfirrmann classification (r=0.413; p=0.014) was found but the correlation coefficient was small. The results of this study demonstrate that there is a correlation between the area of the chondrons and the clinical and imagistic characteristics. The Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) correlated with the chondrocyte area in the presence of a lumbar disc herniation with surgical indication. It should be taken into account that the variables considered only correspond to certain patients with degenerative lumbar discopathy.

Corresponding author: Roxana Folescu, Senior Lecturer, MD, PhD; e-mail:; Dinu Vermesan, MD, PhD; e-mail:

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31. Age and individual anatomical variability of intercostal nerves in human fetuses

Tatyana Vladimirovna Khmara, Ilya Ilyich Okrym, Igor Ivanovich Zamorskii, Svitlana Dmytrivna Novychenko, Olena Yurivna Hahen, Ivan Ivanovich Dronyk

Performing fetal operations on the walls of the thorax and abdomen requires detailed information dealing with the anatomical variability of the intercostal nerves (IN) in human fetuses. Therefore, our study aimed at determining the topographic and anatomical characteristics of the I-XII IN during the period of human ontogenesis. The study involved 70 specimens of fetuses aged 4-10 months, by means of macromicroscopic preparation, superficial staining of dissected vessels and nerves and morphometry. The variability of the topography and asymmetry of the trunks of IN and their branches were revealed. The direction of the lateral musculocutaneous branches of the inferior IN does not coincide with the direction of the muscle bundles of the external abdominal oblique muscle. The branches of the I IN are functionally different, since the superior branch branches out in the skin and vessels, and the inferior one - in the stratum of the internal intercostal muscle. The anterior musculocutaneous branches of the II-VII IN occur in the front of the parasternal neurovascular bundle and are related with each other, with parasternal nerve or with the nerve plexus of the internal thoracic artery. The trunks of adjacent IN relate to one another by means of rare connecting branches, numerous and diverse in shape links are observed between the anterior and lateral musculocutaneous branches of the VIII-XII IN in the area of the anterior-lateral regions of the abdominal wall. The connecting branches descend from the nodes of the thoracic section of the sympathetic trunk to the IN.

Corresponding author: Tatyana Vladimirovna Khmara, Professor, DSc, MD, PhD; e-mail:

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32. Effects of ethanol, nicotine and caffeine gestational exposure of female rats on lung and brain tissues in fetuses: morphological and biological study

Daniela Pintican, Stefan Strilciuc, Sebastian-Mihai Armean, Dan Mihu

Aim: The purpose of this study was to evaluate the implications of toxic exposure on pregnancy, by exploring the oxidant-antioxidant balance and the histopathological (HP) changes of fetal organs. Materials and Methods: Our study was performed on fetuses of gestating rats exposed to ethanol, nicotine and caffeine. HP tissue analysis of fetuses brain and lung samples were performed. Brain and lung homogenates were quantitatively analyzed to determine the oxidant-antioxidant balance [malondialdehyde (MDA), protein carbonylation (PC), glutathione (GSH) and thiol groups (-SH)]. Results: An increase in cerebral pro-oxidant capacity was observed for alcohol exposure groups through increased MDA levels (p<0.001), as compared to controls. An increase in pulmonary and cerebral pro-oxidant capacity was observed for nicotine and caffeine study groups, through increased PC levels (p<0.001). Lower GSH levels indicate a decrease in brain antioxidant defenses in alcohol, nicotine and caffeine groups. Alcohol and nicotine exposure in pregestational and gestational periods caused neuronal hypoplasia in hippocampus and brainstem congestion. Caffeine registered negligible differences as compared to controls. Conclusions: In our experimental model for gestational exposure to chemical agents, alcohol was the strongest teratogenic agent in rat brain samples. No significant changes were observed in lung samples. Results indicate an increase in oxidative stress as a result of alcohol and nicotine consumption during gestation in rats.

Corresponding author: Stefan Strilciuc, MPH; e-mail:

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33. Craniofacial morphology aspects in children with isolated growth hormone deficiency - a cephalometric study

Smaranda Adelina Preda, Dana-Maria Albulescu, Mihaela-Roxana Mitroi, Mihaela Popescu, Florina Nechita, Adrian Camen, Ioana Adina Cotoi

Craniofacial and dental morphology is influenced by different circulating hormones, but it is of particular importance that there is growth hormone (GH) in normal craniofacial and teeth development. Craniofacial morphometry studies in children with GH deficiency show different changes in certain anthropometric variables in the sense of reducing their values compared to normal children s developmental norms in different stages of childhood and adolescence. Therefore, the early establishment of GH replacement therapy can correct craniofacial morphological changes induced by GH deficiency. In our study, we evaluated different anthropometric craniofacial variables at children with GH deficiency and we established some anthropometric and morphological characteristics associated with this pathology.

Corresponding author: Adrian Camen, Associate Professor, DMD, PhD; e-mail:; Florina Nechita, Lecturer, PhD; e-mail:

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34. An unusual onset of Crohn s disease with oral aphthosis, giant esophageal ulcers and serological markers of cytomegalovirus and herpes virus infection: a case report and review of the literature

Sergiu Marian Cazacu, Mirela-Corina Ghilusi, Elena Tatiana Ivan, Bogdan Silviu Ungureanu, Tudorel Ciurea, Adrian Saftoiu, Cristiana-Iulia Dumitrescu, Maria Fortofoiu, Ion Alexandru Vaduva, Carmen-Daniela Neagoe

Isolated esophageal ulcerations in Crohn s disease pose a great challenge in diagnosing and providing the correct treatment. We present the case of a 23-year-old woman with recurrent episodes of oral aphthosis, dysphagia, odynophagia and heartburn. Upper digestive endoscopy revealed an irregular mucosa with multiple ulcerations with irregular margins within the mid-esophagus. Immunoglobulin G (IgG) for cytomegalovirus and herpes virus were both positive. Four years after, she presented with the same symptoms and the involvement of ileo-colonic lesions, with pathological findings helped establish the Crohn s disease diagnosis. Crohn s disease represents an idiopathic chronic inflammatory gut disease, which can affect any part of the digestive tract. The onset by esophageal disease and no intestinal involvement is rare and challenging for a proper diagnosis.

Corresponding author: Bogdan Silviu Ungureanu, MD, PhD; e-mail:; Cristiana-Iulia Dumitrescu, Lecturer, MD, PhD; e-mail:

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35. Impact of genetic testing and family health history of cystic fibrosis in the early prenatal diagnosis and prevention of a new case of genetic disorder

Cristina Crenguta Albu, Ioana Georgeta Stancu, Liliana Georgiana Grigore, Dinu Florin Albu, Stefan Dimitrie Albu, Anca Patrascu, Alexandru Marian Goganau

Cystic fibrosis (CF) is a multi-system autosomal recessive disorder, results of mutations in the CF transmembrane conductance regulator (CFTR) gene, located on the long arm of chromosome 7. We present a special family couple with particular medical history of CF, who comes to our Clinic for genetic tests and a prenatal genetic counseling, to prevent the birth of a new affected CF child. Genetic analysis showed that the first affected child, a daughter, is compound heterozygous for two clinically significant recessive mutations: c.1521_1523delCTT; p.Phe508del, inherited from her mother, who carries the same CFTR mutation, and c.1853_1863delTTTTGCATGAA; p.IIe618Argfs 2, inherited from her father, who is heterozygous, healthy carrier, for the same CFTR mutation. In our case report, early prenatal genetic testing, pre- and post-test genetic counseling was crucial in the management of the present pregnancy, to prevent the birth of a new affected CF child.

Corresponding author: Cristina Crenguta Albu, Lecturer, MD, PhD; e-mail:

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36. Choroidal melanoma, unfavorable prognostic factors. Case report and review of literature

Mihaela Cristiana Coroi, Amine Bakraoui, Cristian Sala, Ovidiu Tica, Otilia Anca Tica, Maria Claudia Jurca, Alexandru Daniel Jurca, Larisa Bianca Holhos, Andrei-Theodor Balasoiu, Liana Todor

Uveal melanoma is the most common intraocular tumor characterized by increased metastatic potential. The tumor develops from uveal melanocytes that, from an embryological point of view, derive from the cells of the anterior neural crest. The risk factors associated with melanoma development are close related to patient phenotype: light-colored hair and iris, fair skin. Recent studies have shown the link between choroidal melanoma and choroidal pigmentation of white-haired and light-colored eyes individuals. Increased pigmentation of the choroid is associated to marked increase in melanocyte density, which from a histological point of view can be a starting point for choroidal carcinogenesis. This case report is about a 36-year-old patient who presented in an outpatient ophthalmological examination for intermittent vision blurring. The ophthalmological examination revealed a view of 0.8 and nasally from the optic nerve head, a prominent tumor-shaped formation was detected during the fundus examination. The presence of a choroidal melanoma was suspected and eye ultrasound, angio-fluorography, optical coherence tomography (OCT) were performed and confirmed the diagnosis. Due to the small size, a team of three ophthalmologists decided to make brachytherapy. The procedure consisting of brachytherapy was temporarily applied to the scleral wall and was done at Debrecen University Hospital, Hungary, the follow-up monitoring being done at the Clinic in Oradea, Romania. Although the initial prognosis was optimistic, after four years of brachytherapy the tumor recurred, the dimensions found were over 14 mm, which is why enucleation was decided. Prior to enucleation, no computed tomography (CT) metastases were detected. Five months after enucleation, hepatic metastases occurred and after another two months, death occurred.

Corresponding author: Maria Claudia Jurca, Lecturer, MD, PhD; e-mail:; Larisa Bianca Holhos, Assistant Professor, MD; e-mail:

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37. Right hepatectomy extended to segments I and IVa and segmental colectomy performed in the same operative time - case presentation

Octavian Marius Cretu, Laurentiu Vasile Sima, Radu Gheorghe Dan, Emil Florin Hut, Ramona Gidea, Mihnea Munteanu, Ion Paun, Stelian Stefanita Mogoanta

Colorectal cancer remains an important cause of morbidity and mortality worldwide. We present the case of a 58-year-old male patient admitted in Timisoara Hepato-Biliary-Pancreatic Surgical Center, Romania, with transverse colon cancer and synchronous liver metastases, who underwent a major hepatectomy and a segmental colon resection performed in the same operative time. The patient had a postoperative outcome without major complications and with no signs of local or distant recurrence at 15 months postoperatively. Conclusions: The synchronous approach of both the primary tumor and liver metastases in colorectal cancer is a possible therapeutic method, even in the case of major hepatectomies.

Corresponding author: Laurentiu Vasile Sima, Lecturer, MD, PhD; e-mail:

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38. Complex regional pain syndrome as a paraneoplastic disorder associated with metatypical basal cell carcinoma

Cristina-Elena Gofita, Marius Eugen Ciurea, Stefan Cristian Dinescu, Ananu Florentin Vreju, Loredana Elena Stoica, Raluca Niculina Ciurea, Mihail Virgil Boldeanu, Otilia Constantina Rogoveanu, Magdalena Rodica Traistaru, Ana-Maria Bumbea, Paulina Lucia Ciurea, Anca Emanuela Musetescu

Metatypical basal cell carcinoma (MTBCC) is a rare form of tumor, which associates the clinical and histopathological (HP) characteristics of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with a 5% chance for the development of metastases. The reference diagnosis remains the HP confirmation from the lesional tissue. The current report illustrates the case of a 74-year-old patient, diagnosed with MTBCC consequently to the biopsy from the clinically malignant lesion with HP and immunohistochemical examination, currently in clinical remission following surgical treatment. The musculoskeletal symptoms represent the patient s admission reason to the Clinic of Rheumatology, where he was diagnosed with paraneoplastic type I complex regional pain syndrome (CRPS-I). The onset was six weeks prior with intense pain in the upper limb, burning sensation and nondermatomal distribution, exacerbated by lowering the position of the upper limb. The clinical evaluation revealed vasomotor disorders: color changes on the skin of the upper limb, venous turgescence on the back of the hands, and local increased temperature. Also, there were evident sudomotor modifications with hyperspiration and fluffy edema. The presence of clinical manifestations associated with the HP confirmation of MTBCC and the information provided by the imaging tests regarding the evaluation of tumor extension advocates for the diagnosis of paraneoplastic CRPS, consequently to both the primary tumor and the pulmonary metastasis. Diagnosis of CRPS-I is generally established on the basis of clinical criteria after excluding other conditions that may explain the degree of pain and the existing dysfunction. The therapist should be aware of the clinical manifestation of CRPS, as early recognition and aggressive treatment often leads to the best response.

Corresponding author: Marius Eugen Ciurea, Professor, MD, PhD; e-mail:

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39. Giant abdominal tumor - would you think adrenal?

Irina Tica, Vitalie Morosan, Luminita-Gentiana Micu, Costin Niculescu, Mihaela-Cezarina Mehedinti, Malina Coman, Stefania Craitoiu, Monica Mihaela Iacov-Craitoiu, Vlad-Iustin Tica, Zizi Niculescu

Adrenal cavernomas are rare benign tumors, and those of giant dimensions are exceptional. Usually, they are symptomless or they induce symptoms and signs due to compression over nearby organs. We present the case of a 68-year-old woman, who complained of abdominal enlargement and abdominal pain in the left part of the abdomen. Imagistic investigations (native and contrast abdominal computed tomography) revealed an inhomogeneous retroperitoneal mass of 210/182/200 mm, containing calcifications. Laboratory findings were not relevant, just a slight and non-significant elevation of carcinoembryonic antigen and a slight elevation of C-reactive protein. Diagnosis of cancer of undetermined origin was considered, and surgery was performed. During surgery, a giant encapsulated inhomogeneous tumor of 330 mm, with cystic areas, was removed, without assessing the origin. Primary or secondary tumors (metastasis from breast, intestinal, lung, renal or skin cancer) were taken into account. Only histopathology and immunohistochemistry revealed the diagnosis of adrenal cavernoma. Until this moment, we found only one published article in the medical literature with similar dimensions of an adrenal cavernoma as in our case. Even if rare, hemangioma of the adrenal gland must be considered during the differential diagnosis of an adrenal tumor.

Corresponding author: Vlad-Iustin Tica, Professor, MD, PhD; e-mail:

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40. A comprehensive evaluation of an OFDI syndrome from child to teenager

Valerica Belengeanu, Diana Marian, Tiberiu Hosszu, Alexandru Simion Ogodescu, Alina Draga Belengeanu, Christian Samoila, Paul Freiman, Ioana Elena Lile

Orofaciodigital syndrome (OFDS) is a collective term for a rare inherited disorder that displays a wide phenotypic and genetic heterogeneity. The findings of diagnostic are the combination of the characteristic oral, facial and digital anomalies. In this heterogeneous group, the diagnosis of OFDI focuses on the association of the oro-dental, digital and cerebral malformations, polycystic kidney disease and several other manifestations. In this article, we report and discuss the case of a girl with OFDI syndrome, who presented as a peculiar phenotype on clinical examination. The present case was diagnosed at 24 months old and re-examined at 16 years old. The imagistic and cephalometric analyses were performed to investigate the alterations in the facial and skeletal bones and also neurological, renal and dental development. The differential diagnosis of this entity is discussed.

Corresponding author: Diana Marian, Lecturer, DMD, PhD; e-mail:; Paul Freiman, Associate Professor, DMD, PhD; e-mail:

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41. Breast myeloid sarcoma after allogeneic stem cell transplantation for acute myelomonocytic leukemia - case report

Lucia Bubulac, Alexandru Bardas, Delia Codruta Popa, Ecaterina Didona Vasilache, Bogdan Octavian Ionescu, Daniel Coriu, Zsofia Varady, Camelia-Marioara Dobrea

Defined as a rare extramedullary tumor, myeloid sarcoma (MS) is in the attention of specialists, although the information in the literature is represented especially through case reports. MS can precede acute myeloid leukemia (AML), appear simultaneous and can be the only manifestation of leukemia relapse after allogeneic stem cell transplantation (allo-SCT). We present the case of a 30-year-old female diagnosed with acute myelomonocytic leukemia (AML M4), with complete remission (CR) after chemotherapy, followed by allo-SCT for consolidation. After five months, the patient presented right breast tumors. Ultrasound-guided biopsy of the breast lesion displayed diffuse infiltration of undifferentiated tumor cells, with blastic granulocytic features, strongly immunopositive for cluster of differentiation (CD) 45, CD99, CD34 and myeloperoxidase (MPO) and negative for all epithelial markers [MNF116, cytokeratin 7 (CK7), estrogen receptor (ER), progesterone receptor (PR), E-cadherin]. The final diagnosis was AML relapse with breast MS. After multiple leukemia relapses with breast MS, the patient died with cerebral bleeding secondary to severe thrombocytopenia.

Corresponding author: Lucia Bubulac, Assistant Professor, MD; e-mails:,

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42. Neurofibromatosis type 1 associated with moyamoya syndrome. Case report and review of the literature

Magdalena Budisteanu, Carmen Magdalena Burloiu, Sorina Mihaela Papuc, Ina Ofelia Focsa, Dan Riga, Sorin Riga, Aurora Arghir

Neurofibromatosis type 1 (NF1) is a genetic disorder with a very heterogeneous clinical picture, affecting central nervous system, skin and bone system. Cerebrovascular lesions, such as moyamoya syndrome, are rarely seen in NF1. Approximately 250 children with NF1 and moyamoya syndrome have been reported. The clinical picture includes hemiparesis, hemianopsia, paresthesia, seizures, speech disorders, and intellectual disability. In this paper, we report on a 6-year-old girl with NF1 and moyamoya syndrome, with a brief review of the existing literature.

Corresponding author: Magdalena Budisteanu, Associate Professor, MD, PhD; e-mail:

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43. Concomitant lung and intestinal tuberculosis - case report

Floarea Mimi Nitu, Cristina Calarasu, Roxana Maria Nemes, Letitia Adela-Maria Streba, Alexandra Floriana Nemes, Madalina Olteanu, Andreea-Loredana Golli

Tuberculosis (TB) is responsible for one in five deaths for young women (between 15-44 years old). Almost 9 million persons are diagnosed with TB each year and around 2 million deaths are due to TB or TB complications. Abdominal TB has no specific clinical symptoms, no imagistic and no specific laboratory tests, all these making the diagnosis more difficult. Most often, clinical, radiographic, and histopathological (HP) aspects in TB enteritis are nonspecific and may suggest cancer or inflammatory bowel disease. We present the case of a 42-year-old male patient, with intestinal and lung TB presenting as intestinal obstruction to emphasize the importance of clinical suspicion and histopathology for final diagnosis. Chest and abdomen computed tomography (CT) evidenced a few left-sided pulmonary nodules and wall thickening of some parts of the small and large bowel. Also, CT evidenced nearby mesenteric lymphadenopathy. He was admitted in the Department of Surgery and later confirmed with intestinal TB. Because of modified chest radiography, further investigations identified Mycobacterium tuberculosis in the sputum. Final diagnosis was concomitant lung and intestinal TB confirmed by sputum and histopathology. The patient received proper anti-tuberculous treatment and his condition improved after the first month. The physician treating the organ is the one that should establish the diagnosis of extra-respiratory TB; however, treatment and later follow-up are multidisciplinary. TB should always be suspected in any patient with nonspecific symptoms. The TB case is defined according to disease localization, bacteriological or HP confirmation, therapeutic history and human immunodeficiency (HIV) infection status.

Corresponding author: Madalina Olteanu, Lecturer, MD, PhD; e-mail:

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44. Key regulations related to stem cell research

Maria Aluas, Doina Adina Todea, Claudia Diana Gherman

Medicine is an ever-changing science. Stem cell research is nowadays part of the medicine. After developments and trials for decades, in 1988 it was announced that a variety of diseases and injuries would be cured with new stem cell therapy, such as: cancer, diabetes, Parkinson s, spinal cord injuries and many others. After almost 10 years of research in the field, in 2007 other good news and hopes were announced: the possibility to create induced pluripotent stem cells, derived from somatic cells, easily used to establish any disease-specific cell line. And research is going on. In order to find answer to a variety of challenges in this area, a researcher faces the following main question: Which are the legislations and the normative standards to be taken into account when we are supposing to conduct a research on/with stem cells? The purpose of the paper is: (i) to familiarize professionals with the current steps in the evolution of stem cell research; (ii) to provide main legal orientations related to stem cell research; (iii) to indicate limits and explanations on legal regulations related to the research on stem cells.

Corresponding author: Maria Aluas, Lecturer, PhD; e-mail:

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45. Ethical assessment of the EU health policy under the Directive 2011/24/EU: approaching patients rights and cross-border healthcare

Anca Parmena Olimid, Daniel-Alin Olimid

Purpose: The purpose of the present article is to discuss the ethical challenges of the European Union (EU) health legislation framing the patients rights and the cross-border healthcare (CBHC). Background: The paper reviews the EU main legislation in the field, namely the Directive 2011/24/EU (CBHC Directive) of the European Parliament and of the Council of 9 March 2011, on the application of patients rights in CBHC. Content: The aim of the study is to analyze the patients rights and the CBHC, enhancing the healthcare support and coordination under this regulatory framework. An exploratory and descriptive analysis will be conducted based on these legal provisions by focusing the ethical choices, the ethical duty, the ethical reasons and the patients rights. An introductory literature overview will be provided and an analysis of the recent data reports published by the European Commission (EC) on the application of the CBHC Directive will be detailed. Therefore, six main themes emerged: (i) the protection of the patients rights; (ii) the examination of the ethical challenges to address the EU public health issues; (iii) the monitoring of the data reports on the operation of the CBHC Directive; (iv) the reimbursement of costs of CBHC; (v) the European reference networks (ERNs); (vi) the eHealth network and the health technology assessment (HTA). Conclusions: The paper reviews the existing legal framework aimed to support the Member States (MS) in achieving a harmonized implementation of the CBHC Directive. Hence, particular ethical issues will be developed under this regulatory framework.

Corresponding author: Anca Parmena Olimid, Associate Professor, PhD; e-mail:

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46. Letter to the Editor: May transdisciplinarity be the new paradigm for current Embryology? A proposal for debating

Alberto Enrique D Ottavio


Corresponding author: Alberto Enrique D Ottavio, PhD; e-mail:

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