ROMANIAN JOURNAL of MORPHOLOGY and EMBRYOLOGY

Vol. 57 No. 3, 2016

1. Pointing at Ito cell, from structure to function (or Cinderella story in liver histology)

Adriana Grigoras, Simona Eliza Giusca, Elena Roxana Avadanei, Cornelia Amalinei, Irina-Draga Caruntu

For more than 130 years, the hepatic stellate cells (also known as Ito cells) have been the object of numerous studies that aimed at their characterization both in normal and postlesional status, where they play a key role in fibrosis progression specific for chronic hepatic pathology. Converged studies on their histophysiology have revealed other functions, namely the involvement in liver embryological development and regeneration, metabolisms regulation, modulation of local inflammatory and immune reactions. Ito cells plasticity is surprising, as they are able to provide the connection between the complex sinusoidal and parenchymal microenvironment, influencing by autocrine and paracrine mechanisms the extracellular matrix content in tight correlation to growth and repair necessities. Last but not least, Ito cells take an active part in systemic homeostasis maintenance by their capacity to store and mobilize vitamin A, respectively. The evolving interest in their research will be undoubtedly followed by a better knowledge of the physiopathological sequences responsible for liver diseases, as new targets for the development of new therapeutic approaches directed toward improvement of prognosis and patients quality of life.

Corresponding author: Irina-Draga Caruntu, Professor, MD, PhD; e-mail: irinadragacaruntu@gmail.com

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2. The utility of bone remodeling markers in the diagnosis, evolution and treatment response evaluation in bone metastases

Mihail-Lazar Mioc, Horia George Haragus, Andrei Dan Balanescu, Pompiliu Horatiu Petrescu, Mihaela Iacob, Radu Prejbeanu

After the lungs and liver, the bone is the third most common site for metastatic disease, appearing frequently in breast and prostate malignancies. These pathological bone events that occur during the evolution of the metastatic disease are usually the onset of osteolysis and they lower the patient s life quality, and are sometimes the cause of death due to the required treatments (surgery, radiotherapy). Due to the nature of the bone remodeling process, the markers that control bone resorption are the main early indicators of bone malignancy. These markers can be found in excess quantities of 50-150% in patients with bone metastases. Analyzing these indicators in conjunction with traditional tumoral markers such as the prostate specific antigen (PSA) and the type I collagen cross-linked telopeptide (ICTP) can often increase the sensibility of the investigation and the chances of diagnosing bone metastases. The studies that were carried out in order to research this area of knowledge have had good and expected results. Most of the efforts are now channeled into developing a better therapeutic strategy that would allow for the early diagnosis and treatment of the pathological bone events. Until these markers can be used as standard investigation methods in all of our patients, some controlled studies must be carried out in order to statistically prove these results, which are purely observational.

Corresponding author: Pompiliu Horatiu Petrescu, Assistant Professor, MD, PhD; e-mail: lalusha87@yahoo.com

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3. Narrow band imaging endoscopy for detection of precancerous lesions of upper gastrointestinal tract

Dan Nicolae Florescu, Elena Tatiana Ivan, Adriana Mihaela Ciocalteu, Ioana Andreea Gheonea, Diana Rodica Tudorascu, Tudorel Ciurea, Dan Ionut Gheonea

Gastric cancer (GC) is an important health problem despite the advances in surgery and chemotherapy and although the incidence is decreasing, GC is still considered the second most common cause of deceases produced by cancer. Survival rates in gastric cancer are low, mainly because most patients are often diagnosed in late stages. The current interest in the diagnostic of GC is the detection of early gastric cancer. Advances in high-resolution endoscopic techniques such as narrow band imaging (NBI) allow the detection of early precancerous lesions like polyps or metaplastic mucosa. Performing only white light imaging endoscopy in order to detect gastric cancer can lead to omission or misdiagnose of a considerable number of early gastric cancers. NBI endoscopy associated with other high-resolution examinations is viable in detecting early gastric cancer, though few studies also indicate that the endoscopist s expertise plays an important factor as well.

Corresponding author: Ioana Andreea Gheonea, MD, PhD; e-mail: iagheonea@gmail.com

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4. Histopathological aspects in autoimmune cutaneous manifestations associated with hepatitis C virus infection

Laura Statescu, Dan Vata, Delia Ciobanu, Laura Gheuca Solovastru, Maria Rotaru

Autoimmunity is characterized by activation of the immune system that attacks and destroys wrongly, the body s own structures. All body tissues can be affected (erythrocytes, leukocytes, platelets, blood vessels, muscle tissue, endocrine system, and other), including the skin. Autoimmune diseases have an increased frequency in women, especially in adulthood, and they are associated with hereditary factors. Although the etiology of autoimmune diseases is incompletely elucidated, there is an association between chronic infection with hepatitis C and autoimmunity, association highlighted and well documented in clinical studies. Other viral infections do not have the same connotation in the context of autoimmunity, but it is recognized that they are an important triggering factor in the pathophysiological mechanism. The cases associating chronic hepatitis C treated with interferon and ribavirin, with multiple autoimmune diseases substrate, raising the discussion of a possible pathophysiological correlation between them.

Corresponding author: Dan Vata, Assistant Professor, MD, PhD; e-mail: dan.vata@umfiasi.ro

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5. Peritumoral inflammatory reaction in non-melanoma skin cancers - histological and immunohistochemical study

Ioan Avramoiu, Ileana Octavia Petrescu, Marius Eugen Ciurea, Adriana Bold, Isabela Silosi, Marilena Monica Tantu, Mihaela Niculescu, Rumi Eugen Anghel Savciu, Stelian Stefanita Mogoanta

Non-melanoma skin cancers (NMSCs) are the most frequent types of cancer in white skin populations, all over the world. In the last 40 years, there was observed a rapid increase of their incidence, because of the UV radiations exposure and weather changes. Although its morbidity is a relatively modest one, the direct social costs of NMSCs are quite substantial due to a high incidence. Due to these reasons, numerous studies try to clarify the etiopathogenic mechanisms of NMSCs, to elaborate treatment and prevention measures. In the last years, a special attention was given to the relation between inflammation and skin cancer. In our study, we performed a histological and immunohistological evaluation of the inflammatory reaction on a number of 73 surgical exeresis pieces coming from the patients diagnosed with NMSCs. Of these, 21 were squamous cell carcinomas (SCCs) and 52 basal cell carcinomas (BCCs). The peritumoral inflammatory reaction in NMSCs was an extremely variable one in intensity and distribution, from one case to another and even from one area to another within the same tumor, thus proving the complexity of the relations between tumor cells and the cells of the immune system. By comparing the intensity of the inflammatory reaction between the two main types of NMSCs, there was observed that in SCCs the inflammatory reaction was more intense in comparison to BCCs. Also, in SCC there was highlighted a more abundant inflammatory infiltrate in poorly differentiated carcinomas, in comparison to the well-differentiated ones. The presence of the immune system cells (T-lymphocytes, macrophages, mast cells) among the tumoral cells, in a direct contact with these, makes us believe that between the two categories of cells there may appear mechanisms of intercellular communication, distinct from the mechanisms of paracrine signaling.

Corresponding author: Marius Eugen Ciurea, Professor, MD, PhD; e-mail: meciurea@gmail.com

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6. Caspase 3 expression and plasma level of Fas ligand as apoptosis biomarkers in inflammatory endotoxemic lung injury

Raluca-Stefania Fodor, Anca-Meda Georgescu, Bianca-Liana Grigorescu, Adrian-Dan Cioc, Mihaly Veres, Ovidiu-Simion Cotoi, Pal Fodor, Sanda-Maria Copotoiu, Leonard Azamfirei

Objective: The objective of this study is to evaluate if the immunohistochemical expression of a pulmonary apoptosis marker and plasma level of Fas ligand (FasL) correlates with the dose- and time-dependent severity of lung injury, induced by the administration of lipo-polysaccharide (LPS) in an endotoxemic rat model. Materials and Methods: Our study included 30 male Wistar rats, randomly divided into three groups: one control group (n=6) and two experimental groups (n=12/group), in whom we induced endotoxemia by intraperitoneal injection of progressively increasing doses of LPS (5, 10 mg/kg). We measured FasL plasma levels of the rats at different time points and analyzed the relationships with markers of lung injury. To investigate the level of caspase 3-protein expression, the immunohistochemistry of the lung tissue was assessed. Results: The median percentage of caspase 3-stained cells for the 5 mg/kg LPS dose was 0.36%, for the 10 mg/kg LPS dose was 0.4% and for the control group was 0.03% (p<0.0001). The elevated expression levels of caspase 3 were consistent with the altered lung morphologies observed (rs=0.88). LPS administration in rats resulted in a significant dose-dependent increase in the levels of plasma FasL (p<0.0001). These levels correlated with markers of lung injury: degree of hypoxemia (rs=-0.42), histological measured lung injury score (rs=0.72), the density of the caspase 3 staining cells in the immunohistochemistry assessment of apoptosis (rs=0.81) and with the plasma RAGE (receptor for advanced glycated end-products) values (rs=0.70). Conclusions: Apoptosis is increased in edotoxemia induced lung injury and is likely to contribute to alveolar injury.

Corresponding author: Anca-Meda Georgescu, Associate Professor, MD, PhD; e-mail: ancameda.georgescu@umftgm.ro

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7. The prognostic and clinical significance of neuroimagistic and neurobiological vulnerability markers in correlation with the molecular pharmacogenetic testing in psychoses and ultra high-risk categories

Laura Alexandra Nussbaum, Lavinia Maria Hogea, Nicoleta Ioana Andreescu, Raluca Claudia Gradinaru, Maria Puiu, Andrei Todica

We approach an integrated, multidisciplinary, innovative research-action model in children and adolescents with psychosis and ultra high-risk categories. Our main focus was: to investigate the prognostic and clinical significance of neuroimagistic and neurobiological vulnerability markers in correlation with the molecular pharmacogenetic testing in psychoses and ultra high-risk categories; the dynamic evaluation of the clinical evolution for the studied groups in correlation with specific neurobiological and neuroimagistic variables and markers. Our research was conducted in the period 2009-2015 on 87 patients, children and adolescents with psychosis (42 took treatment after pharmacogenetic testing, 45 without) and 65 children with ultra high-risk (UHR) for psychosis - 32 benefited of pharmacotherapy after pharmacogenetic testing and 33 without. Also, the patients were evaluated through magnetic resonance (MR) spectroscopy at baseline and after pharmacotherapy. The efficacy of the chosen therapy in correlation with the pharmacogenetic testing was evaluated through the mean change in the Positive and Negative Syndrome Scale (PANSS) total scores, in the Clinical Global Impression of Severity and Improvement (CGI-S/I), Children s Global Assessment Scale (CGAS) and through the change registered for the relevant neurobiological markers and MR spectroscopy metabolites, from baseline until endpoint in different timepoints. Our results, showed statistically significant differences of the clinical scores between the studied groups. Our research was a proof, sustaining the use of the pharmacogenetic testing in clinical practice and the value of investigating relevant neurobiological and neuroimagistic markers for a personalized, tailored therapy for psychotic patients and neuro-psychiatric UHR categories, as a fruitful pathway of intervention and care.

Corresponding author: Lavinia Maria Hogea; e-mail: laviniahogea@yahoo.com

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8. Pharmacotoxicological screening on new derivatives of beta-phenylethylamine, potential agonists of beta3-adrenergic receptors

Simona Negres, Anca Zanfirescu, Floriana Elvira Ionica, Elena Morosan, Bruno Stefan Velescu, Oana Cristina Seremet, Cristina Elena Zbarcea, Emil Stefanescu, Manuella Militaru, Andreea Letitia Arsene, Denisa Marilena Margina, Livia Uncu, Corina Scutari, Cornel Chirita

Background and Aims: Beta3-adrenergic receptors (beta3-ARs) have been initially characterized in 1989. Afterwards, their tissue distribution was established: white and brown adipose tissue, central nervous system, myocardium (atrial and ventricular), blood vessels, smooth gastrointestinal muscles (stomach, small intestine, colon), gallbladder, urinary bladder, prostate, skeletal muscles. Non-clinical trials have demonstrated the major implication of beta3-ARs in glucose metabolism, implicitly, in insulin release, and also in obesity. Therefore, new compounds were synthesized starting from beta-phenylethylamine nucleus and substituted in various positions, for possible antidiabetic and/or antiobesity action. Materials and Methods: In the present research, the antidiabetic action of newly synthesized compounds was investigated on an experimental model of alloxan-induced diabetes, administered in dose of 130 mg/kg body weight (bw), intraperitoneally (i.p.). After 14 days of treatment, glycemia and enzymes involved in homeostasis of glucose metabolism, glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase (G6Pase) and hexokinase were determined. Animals were then euthanized and histopathology examinations were performed on harvested liver, kidney, spleen and brain in order to document pathological changes induced by alloxan-induced diabetes and/or by tested compounds. Results and Conclusions: Glycemia in animals treated with the tested compounds decreased statistically significant for groups C2 and C3 (-42.13% and -37.2%, respectively), compared to diabetic control group. C2 was also the compound to favorably modify the dynamics of determined enzymes, together with the display of very good safety profile supported by minor, non-significant, histopathological changes.

Corresponding author: Floriana Elvira Ionica, Lecturer, Pharm, PhD; e-mail: floriana_umf@yahoo.com

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9. A computer-aided diagnostic system for intestinal polyps identified by wireless capsule endoscopy

Adriana Florentina Constantinescu, Mihaela Ionescu, Vlad-Florin Iovanescu, Marius Eugen Ciurea, Alin Gabriel Ionescu, Costin Teodor Streba, Marius-Gabriel Bunescu, Ion Rogoveanu, Cristin Constantin Vere

Small bowel polyps present in images acquired by wireless capsule endoscopy are more difficult to detect using computer-aided diagnostic (CAD) systems. We aimed to identify the optimum morphological characteristics that best describe a polyp and convert them into feature vectors used for automatic detection of polyps present in images acquired by wireless capsule endoscopy (WCE). We prospectively included 54 patients with clinical indications for WCE. Initially, physicians analyzed all images acquired, identifying the frames that contained small bowel polyps. Subsequently, all images were analyzed using an automated computer-aided diagnostic system designed and implemented to convert physical characteristics into vectors of numeric values. The data set was completed with texture and color information, and then analyzed by a feed forward back propagation artificial neural network (ANN) trained to identify the presence of polyps in WCE frames. Overall, the neural network had 93.75% sensitivity, 91.38% specificity, 85.71% positive predictive value (PPV) and 96.36% negative predictive value (NPV). In comparison, physicians diagnosis indicated 94.79% sensitivity, 93.68% specificity, 89.22% PPV and 97.02% NPV, thus showing that ANN diagnosis was similar to that of human interpretation. Computer-aided diagnostic of small bowel polyps, based on morphological features detection methods, emulation and neural networks classification, seems efficient, fast and reliable for physicians.

Corresponding author: Mihaela Ionescu, Eng, PhD; e-mail: miki.iones@yahoo.com

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10. Lectin purification from carp roe (Cyprinus carpio L.), investigation of its carbohydrate specificity and application in histochemistry

Rostyslav Antonyuk, Alexander Lutsyk, Volodymyr Antonyuk

A method of lectin purification from carp roe (CCRA) was elaborated, which includes affinity chromatography on cross-linked ovomucoid and copolymers of polyvinyl alcohol and blood group-specific substances. That allowed obtaining lectin with electrophoretic purity and yielding of cca. 42 mg/kg roe. Electrophoresis in 15% polyacrylamide gel in the presence of beta-mercaptoethanol showed one band with molecular mass cca. 15 kDa, whereas in the absence of beta-mercaptoethanol, CCRA exposed band with molecular mass cca. 60 kDa. The resulting lectin was thermostable, withstanding heating to 75 degrees C for 15 minutes, without noticeable loss of hemagglutinating activity. Gel column chromatography on Toyopearl HW-55 determined the lectin molecular weight of 120+/-3 kDa. For the lectin activity, divalent metal ions (Ca2+ and Mg2+) were not necessary. CCRA showed the best agglutination titer with pigeon erythrocytes, weaker - with rabbit and dog erythrocytes, and significantly weaker - with human and rat erythrocytes. CCRA lectin was specific to N-acetyl-D-galactosamine and D-galactose group carbohydrates. The best lectin activity inhibition possessed alkaline phosphatase of calf intestine and fetuin. CCRA exposed highest affinity to complex oligosaccharide similar to the receptor of Phaseolus vulgaris erythroagglutinin (PHA-E). A comparative study on the histochemical specificity of CCRA and PHA-E using specimens of normal tissues, and that of colon neoplasia, showed similar, yet not identical binding properties. CCRA lectin rather differentially labeled adenoma and adenocarcinoma of colon, which suggests its prospective applicability in diagnostic histopathology.

Corresponding author: Alexander Lutsyk, Professor, MD, PhD; e-mail: lutsyk@meduniv.lviv.ua, lutsykalexander@gmail.com

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11. Morphological, imaging and surgical aspects in endometrial endometrioid adenocarcinoma

Costin Berceanu, Alex Emilian Stepan, Claudia Mehedintu, Monica Mihaela Cirstoiu, Razvan Ciortea, Sabina Berceanu, Ioana Andreea Gheonea, Elvira Bratila

Endometrioid endometrial adenocarcinomas (EECs) are frequent genital tumors for which the clinical, imaging and histopathological integrated analysis is the basis of differential diagnosis and therapeutic attitude. This research represents a tertiary multicenter study including 58 cases examined histopathologically and immunohistochemically, surgically treated, on a five years period. The main characteristics of the patients in the study group are represented by the average age of 66 years, associated with obesity, hypertension, diabetes, history of infertility, early menopause, nulliparity or long-time oral contraception. The most important clinical sign was the menopausal or postmenopausal vaginal bleeding. The golden standard in the diagnosis of endometrial carcinoma is the dilation and curettage of the uterine cavity, followed by histopathological assessment. The association between transvaginal ultrasonography (TVUS) and endometrial biopsy increases to 100% the diagnostic sensitivity. The use of an antibodies panel that includes CK, ER, PR, vimentin can guide the diagnosis to EEC and the analysis of Ki67, p16, p53 and CEA immunoreactions can be useful both for EEC differential diagnosis and to assess the tumor aggressiveness. The interrelation between the accurate histopathological diagnosis and the adequate surgical staging is the cornerstone of curative therapy in the EEC.

Corresponding author: Alex Emilian Stepan, Lecturer, MD, PhD; e-mail: astepan76@yahoo.com

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12. Experimental animal model in a histological study of drug-induced gingival overgrowth

Adelina Gabriela Bobic, Stefania Craitoiu, Roxana Maria Pascu, Ileana Cristiana Croitoru, Marius Matei, Florian Obadan, Monica Mihaela Craitoiu

Gingival overgrowth (GO) is a pathology with important aesthetic and functional implications and with a multifactorial pathogenesis. Incriminated etiological factors include antihypertensive, antiepileptic and immunosuppressant medication. We aimed to evaluate the induction of gingival overgrowth on experimental rats, depending on the drug type, dose and duration. In the research conducted by us, the increase in gingival tissue production occurred gradually, depending on the administered medication and the time elapsed after its start. The study conducted shows that experimentally induced gingival overgrowth of the administered drugs is made possible by altering tissue homeostasis through altering the fibrocyte cell populations involved in the tissular turnover as well as those involved in the inflammatory process. A better understanding of the pathogenesis of this undesirable effect may lead to the development of improved management strategies for preventing it, or reducing it through non-surgical methods.

Corresponding author: Stefania Craitoiu, Professor, MD, PhD; e-mail: scraitoiu@yahoo.com

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13. Correlations between etiological factors and lesion severity in carotid artery atheromatosis

Cristian Constantin, Dana-Maria Albulescu, Valeria-Carmen Albu, Aniela Raluca Danciu, Andrei-Constantin Deaconu

Occurrence of atheromatous plaques on the internal wall of large and medium sized arteries represents a widely spread disease. It is especially found in the elderly, but also in individuals belonging to the 4th-6th decade of life with an increasing incidence. Correlating the main etiological factors with morphological change severity, in conjunction with settling the importance of each factor on its own in generating and developing arterial plaques, has an important predictive role in the evolution of atherosclerotic pathology. The purpose of this study is to investigate the existence of a correlation between the main factors linked to atheromatosis and the degree of severity of the carotid artery stenosis. This is obtained by ultrasonographic examination of the carotid arteries in correlation with determining serum cholesterol levels, thus ascertaining the risk for atheroma related events and disease progression._x000D_ _x000D_

Corresponding author: Constantin Cristian, MD, PhD; e-mail: stiric@lycos.com

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14. Oral toxicity study of certain plant extracts containing pyrrolizidine alkaloids

Oana Cristina Seremet, Florica Barbuceanu, Floriana Elvira Ionica, Denisa Marilena Margina, Claudia Maria Gutu, Octavian Tudorel Olaru, Mihaela Ilie, Veaceslav Gonciar, Simona Negres, Cornel Chirita

Pyrrolizidine alkaloids (PAs) are a class of toxic compounds which are found in plants. Poisoning caused by these toxins is associated with acute and chronic liver damage. Tussilago farfara (coltsfoot), Petasites hybridus (common butterbur), Senecio vernalis (eastern groundsel) and Symphytum officinale (comfrey) are traditional phytotherapic species, which beside the therapeutic bioactive compounds contain PAs. The aim of the paper was to assess the safety of some dry extracts obtained from these species. For the determination of acute toxicity, Organization for Economic Cooperation and Development (OECD) Guideline No. 423 was used. For the determination of repeated dose oral toxicity, Senecionis vernalis herba and Symphyti radix extracts (250 mg/kg) were administrated, by gavage, for 28 days, and their effects on animal weight, liver and biliary functions, hepatic tissue and oxidative stress were investigated. After the acute toxicity testing, the dry extracts were placed in the GHS Category V (LD50>5000 mg/kg, p.o.). For the subacute toxicity testing, no death or any signs of toxicity were observed. Also, no significant differences in biochemical parameters were observed between control and treated groups. The observed histopathological lesions were non-specific and were not consistent with the data reported in the literature for PAs exposure. In conclusion, the administration for 28 days, of the tested extracts, in a dose which correspond to a PAs concentration over the limits imposed in some countries, produced no hepatic and biliary toxic effects. Further studies, extended over a longer period of time, are needed in order to determine the safety of plant extracts containing PAs.

Corresponding author: Floriana Elvira Ionica, Lecturer, Pharm, PhD; e-mail: floriana_umf@yahoo.com

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15. Correlations between endothelial cell markers CD31, CD34 and CD105 in colorectal carcinoma

Ionela Cristina Deliu, Carmen-Daniela Neagoe, Marinela Bezna, Amelia-Valentina Genunche-Dumitrescu, Sebastian Constantin Toma, Bogdan Silviu Ungureanu, Constantin Daniel Uscatu, Maria Cristina Bezna, Cristian Virgil Lungulescu, Vlad Padureanu, Dan Ionut Gheonea, Tudorel Ciurea, Maria Fortofoiu

Purpose: Colorectal carcinoma is an important cause of mortality worldwide. The fact that tumor growth is dependent on angiogenesis has supported researches for new prognostic parameters and the development of novel therapeutic strategies. Accordingly, we sought to evaluate angiogenesis quantitatively by assessing microvessel density in colorectal cancer. Materials and Methods: The blood vessels stained with CD31, CD34 and CD105 were counted, and we reported their number per square millimeter in order to obtain microvascular density (MVD). Then, we aimed at comparing the performance of three endothelial cell markers (CD31, CD34, and CD105) on formalin-fixed tissues from 58 patients diagnosed with colorectal cancer. Results: Following the comparison of the average effective vessels marked with the three markers, Student s t-test showed that the mean number of blood vessels marked with CD34 is higher than the blood vessels marked with CD31 and CD105. A significant difference that has been registered between the three levels of the T stage was found in the patients in our study, in terms of value marker CD105, ANOVA p=0.049, which returns to a value <0.05. Quick time decreases the pT stage, the observed differences being close to statistical significance. However, the result of ANOVA test does not allow us to say that differences can be generalized and not just a particular result, valid only for the study group, p=0.061 >0.05. There is a significant difference between patients with stage T, in terms of value: hemoglobin (ANOVA p<0.001), hematocrit (ANOVA p<0.001), mean corpuscular volume (MCV) (ANOVA p<0.001), mean corpuscular hemoglobin (MCH) (ANOVA p=0.002 <0.01 - significant difference with 99% confidence). By calculating the Pearson s correlation coefficient for the relationship CD31-CD105, we obtained a value r=0.440, which corresponds to p=0.0013 <0.05, indicating a statistically noteworthy direct correlation between the two factors. Conclusions: CD31 marker increases simultaneously with the CD105, in the cases analyzed throughout the present study. The ability of tumors to maintain a high vascular blood density in their inner portions may represent a reliable parameter to evaluate tumor angiogenesis and a finding relevant for future development of therapeutic angiogenesis strategies.

Corresponding author: Dan Ionut Gheonea, Associate Professor, MD, PhD, MSc; e-mail: digheonea@gmail.com

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16. Clinical, immunological and pathological profile of infants suffering from cow s milk protein allergy

Elena Tataranu, Smaranda Diaconescu, Camelia Geanina Ivanescu, Ioan Sarbu, Maria Stamatin

Cow s milk protein allergy (CMPA) is the most frequently encountered form of food allergy in pediatric patients and occurs secondary to cow s milk proteins (CMP) ingestion. The aim of this study is to define the profile of children suffering from CMPA and to describe the associated pathological findings. The authors performed a retrospective case-control study on 160 infants that presented with CMPA symptoms at Sf. Maria Emergency Clinical Hospital for Children, Iassy, Romania, between January 2013 and January 2015. Fifty-five infants were diagnosed with CMPA (Group 1 - cases group) and 105 had no proven allergy (Group 2 - control group). Mean age of patients, gender distribution and prevalence of premature birth registered no statistically significant difference between the two groups. The prevalence of familial history of allergy was higher in case of patients with CMPA (36.36% versus 20% in control group). The delay between the introduction of CMP into alimentation and symptoms onset was significantly shorter in Group 1 (12 days) compared to Group 2 (42 days) (p=0.0051), thus pleading for an earlier onset of symptoms in case of CMPA. CMPA usually manifested through an association of gastrointestinal (76.36%), cutaneous and mucosal symptoms (70.91%). Specific IgE were positive values in 49 patients with CMPA (89.09%) and 32 patients (30.48%) without CMPA (p<0.001). Endoscopic examinations with tissue sampling were performed in 26 infants with CMPA. Focal erythema, erosions and lymphoid nodular hyperplasia were signaled in 23 cases and eosinophilic infiltration was noticed in 15 cases. In conclusion, specific IgE and pathological changes offer highly reliable methods for CMPA diagnosis.

Corresponding author: Smaranda Diaconescu, Lecturer, MD, PhD; e-mail: smaranda.diaconescu@umfiasi.ro

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17. The cadherin switch assessment in the epithelial-mesenchymal transition of urothelial bladder carcinomas

Andrei Ioan Drocas, Paul Ioan Tomescu, George Mitroi, Petru Octavian Dragoescu, Claudiu Margaritescu, Alex Emilian Stepan, Valeriu Surlin, Stefania Craitoiu, Ileana Drocas, Anca Marilena Ungureanu, Alice Elena Gaman, Adriana Turculeanu, Cristiana Eugenia Simionescu

Introduction: The epithelial-mesenchymal transition (EMT) process is a complex molecular mechanism that is involved in the acquisition of an aggressive, invasive and metastatic phenotype by carcinomas. The cadherin switch consists in the alteration of E-cadherin and N-cadherin expression and is specific for the EMT process. Materials and Methods: This study included 35 cases of primitive urothelial carcinomas investigated in relation with clinicopathological prognostic parameters and expression of E- and N-cadherins in the advancing edge and intratumoral compartments. Results: In both compartments, the immunoexpression of E-cadherin decreased, while that of N-cadherin increased in high grade, deeply invasive, or those cases with lymph node metastases and advanced stages carcinomas, with a negative linear correlation observed between their expression percentage values. In this study, it was observed the presence of cadherin switch

Corresponding author: Alex Emilian Stepan, Lecturer, MD, PhD; e-mail: astepan76@yahoo.com

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18. Primary retroperitoneal seminoma - embryology, histopathology and treatment particularities

Constantin Virgil Gingu, Mihaela Mihai, Catalin Baston, Mugurel Alexandru Crasneanu, Alexandru Vladimir Dick, Vlad Olaru, Ioanel Sinescu

in urothelial carcinomas, the variation of the two proteins immunostaining patterns being higher at the advancing edge. The presence of N-cadherin in intratumoral compartment designated it as actively involved in EMT process. Conclusions: The analysis of cadherins switch can be used to identify superficial urothelial carcinoma with invasion and metastasis potential.

Corresponding author: Constantin Virgil Gingu, Associate Professor, MD, PhD; e-mail: cgingu@gmail.com

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19. Histological assessment of fracture healing after reduction of the rat femur using two different osteosynthesis methods

Tiberiu Paul Neagu, Mirela Tiglis, Cristiana Gabriela Popp, Cristian Radu Jecan

Osteosynthesis using Kirschner (K) wires and plates with screws were compared on the same subject in a previous experimental protocol, but none of them led to fracture healing. We designed a new murine study in order to compare this two methods on different subjects in order to obtain histological proofs of which one is better and to see how limited periosteum removal influence fracture healing. Divided in two equal groups, femoral osteotomies were performed on 30 Brown Norway rats, then reduced using plates and screws in the OPS (osteosynthesis using plates and screws) group and using K-wires in the OIKW (osteosynthesis using Kirschner wire) group. The animals underwent clinical, radiological and histological assessment for eight weeks. The quality of the fracture healing was associated with a higher number of osteocytes/microscopic field at eight weeks. The difference between the groups regarding the number of osteocytes inside lacuna was statistically significant (t-test for equal variances not assumed, p=0.001), which confirms a mean difference of 32 cells/ microscopic field (mf) with a 95% confidence interval of 15-50 cells/mf. In conclusion, limited periosteum removal did not influence negatively fracture healing. Therefore, we considered that osteosynthesis using plates and screws led to better results compared to fracture fixation using K-wires.

Corresponding author: Tiberiu Paul Neagu, Assistant Professor, MD; e-mail: dr.neagupaul@gmail.com

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20. Histopathological consequences of hyperzincemia on rat teeth. Experimental study

Mihaela Monica Scutariu, Iordanis Salamastrakis, Cristinel Ionel Stan, Alin Horatiu Nedelcu, Liviu Ciprian Gavril, Claudia Florida Costea, Ana Maria Dumitrescu, Anca Sava, Elena Sapte

The aim of this study was to investigate the histopathological features of dental pulp in acute zinc (Zn) intoxication and to identify possible physiopathological mechanisms of the lesions. Twelve adult male Wistar rats were divided into two groups, the control one and the exposed group. Each animal from the experimental group received a single dose of zinc chloride (ZnCl2) by intraperitoneal injection. Blood samples were collected from exposed animals at 2, 4, and 6 hours after the injection and plasma Zn concentrations were determined by spectrophotometry. After six hours of observation, the animals were sacrificed and two teeth from every rat were removed. Twelve teeth were processed by standard histological technique using Hematoxylin-Eosin (HE) and Szekely trichrome stainings, and the other twelve were subjected to Schliff cutting-grinding technique. The experimental group showed increased plasma zinc concentration (0.46+/-0.06 mg/L) after two hours and then slightly decreasing values in the next four hours. Undecalcified teeth did not showed any changing into the dentin or enamel structures, but decalcified teeth revealed numerous deposits into the dental pulp, which consisted of red acellular superposed sediments that could be made up of zinc with some plasma protein, or there could be an unknown compound which precipitated under the influence of zinc cation (Zn2+). We can presume that the dental pulp may be an elective place for zinc accretion and so it must be considered a potential target for this metal.

Corresponding author: Anca Sava, Professor, MD, PhD; e-mail: dr.anca.sava.68@gmail.com

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21. Histopathological findings regarding oncological feasibility of laparoscopic versus open approach for rectal cancer: a retrospective study

Ciprian Duta, Sorina Taban, Diana Al-Jobory, Adelina-Roxana Gheju, Romulus-Bogdan Timar, Sorin Dema, Pompiliu Horatiu Petrescu

Worldwide, colorectal cancer is one of the most prevalent malignancies. Due to oncological safety concerns, data regarding the laparoscopic surgical treatment of rectal cancer is scarce. Our study s main aim was investigate the oncological adequacy of laparoscopic surgery in the treatment of rectal cancer by comparing its oncological reliability with the oncological results obtained after open surgery for rectal cancer. In this retrospective study, 80 patients who underwent surgery for rectal cancer, admitted in our Clinic between January 1, 2014-November 31, 2015 were enrolled. The studied group was stratified according to the way of approach chosen: classic surgery (59 cases) and laparoscopic surgery (21 cases), respectively. Based on the histopathological examination, we analyzed the histological grading of rectal neoplasms, TNM staging, resection margins, lymphovascular and perineural invasion and the number of regional lymph nodes identified in the perirectal adipose tissue. The average number of isolated lymph nodes demonstrated non-significant differences between the two types of approaches: 20 lymph nodes in the classical approach versus 18 lymph nodes in the laparoscopic approach (p=0.109). Lymph nodes affected by metastases were associated in the majority of cases with stage IIIB and stage IIIC rectal cancers (100% and 83.3%, respectively). The laparoscopic approach proved to be efficient in terms of reaching oncological resection limits. On the resection specimens extracted by laparoscopic surgery, the residual tumor (R1) was encountered in 5% of the cases versus in 6.7% of the cases after classic surgery. The laparoscopic approach is oncologically feasible in the rectal cancer surgical treatment.

Corresponding author: Diana Al-Jobory, MD, PhD; e-mail: aljobory.diana@yahoo.com

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22. Micro-CT and optical microscopy imagistic investigations of root canal morphology

Emanuela Lidia Craciunescu, Marius Boariu, Ciprian Ionita, Daniela Maria Pop, Cosmin Sinescu, Mihai Rominu, Meda Lavinia Negrutiu

Protecting the root s internal morphology is the first key toward the success of the endodontic treatment. Due to the vast diversity of endodontic space, it is difficult to visualize and to establish the shape and limits of the root canal, especially the morphology of apical area and lateral root canals. Optical microscopy is a classical imagistic investigation method, widely used along classical methods like radiographs that also offer limited information about root morphology and extension of decay. Micro-computed tomography (micro-CT), a modern imagistic investigation method can provide detailed three-dimensional reconstructions of root canal. Micro-CT is a non-invasive method that has the possibility to offer cross-sectional and axial images of the endodontic space. The success of root canal treatment is based on cleaning and shaping. Beyond these two procedures, sealing the endodontic space by respecting its limits is another prerequisite for long-term success of endodontic therapy. Micro-CT can perform three-dimensional reconstruction of the root canal, root canal filling and can provide accurate images of the endodontic space. The assessment of root morphology can be obtained through imagistic invasive optical microscopy and already mentioned non-invasive methods (micro-CT). The aim of this study is to illustrate and analyze the endodontic space, according to its diversity by using micro-CT, a non-invasive imagistic investigation method an also optical microscopy. The two techniques can also provide the extension of carries or demineralized substance on different levels of the root.

Corresponding author: Cosmin Sinescu, Lecturer, MD, PhD; e-mail: minosinescu@yahoo.com

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23. Rare thymic malignancy of B-cell origin - T-cell/histiocyte-rich large B-cell lymphoma

Ileana Octavia Petrescu, Iancu Emil Plesea, Maria Camelia Foarfa, Simona Bondari, Cristina Elena Singer, Elena Madalina Dumitrescu, Razvan Cosmin Pana, Georgeta Ligia Stanescu, Mircea Ovidiu Ciobanu

Aim: T-cell/histiocyte-rich B-cell lymphoma is a rare type of diffuse large B-cell lymphoma reported as involving primarily the thymus only by one paper in the English literature. Case presentation: A four and a half years old boy was admitted, after a sudden onset in the middle of the night, with superior vena cava syndrome, resuscitated cardiac and respiratory arrest and severe coma with Glasgow Coma Scale rate of 3. In spite of intensive treatment, the patient repeated twice the cardiac arrest and died sixteen hours after admittance. The autopsy confirmed the existence of a huge mediastinal mass, revealed by the prior to death computed tomography examination, and the thorough histopatological established the diagnosis of T-cell/histiocyte-rich large B-cell lymphoma of the thymus with renal spread. Discussion: The particularities of the presented case are the primary location of the lesion in the thymus, the age of the patient, very young, the lack of lymph nodes involvement and the rapid development of the disease until death without any possibility of therapeutic specific intervention. Conclusions: The case is the second reported in the literature with primary involvement of the thymus by this rare variant of diffuse large B-cell lymphoma. The histopatological examination is the golden standard for the diagnosis. Any clinical symptom of unexplained fatigue and dyspnea in a child should raise the clinician s suspicion of a mediastinal mass involving the thymus.

Corresponding author: Iancu Emil Plesea, Professor, MD, PhD; e-mail: pie1956@yahoo.com

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24. Redundant plantar skin folds

Laura Otilia Damian, Siao-Pin Simon, Ioana Felea, Carolina Botar-Jid, Bogdan Stancu, Liliana Rogojan, Cristina Ana Maria Pamfil, Adriana Albu, Simona Rednic

A 46-year-old female patient presented with photosensitivity, symmetric arthritis, episodic plantar pain and strikingly redundant plantar skin folds, likely due to lipoatrophy after recurrent episodes of plantar panniculitis. In this context, leukopenia with lymphopenia, thrombocytopenia and positive antinuclear antibodies were revelatory for systemic lupus erythematosus. However, a small cerebriform plantar collagenoma, along with discrete dysmorphic features with downslanting palpebral fissures and mild right ptosis, second and third syndactyly and a larger first right toe since childhood, and early-onset bilateral ovarian cystadenoma, suggested a minimal Proteus syndrome. Genetic confirmation could not be performed. As adipose tissue dysregulation may be a feature of Proteus syndrome, the possible mechanisms leading to localized lipoatrophy in this setting are discussed. This case enlights intriguing links between adipogenesis, inflammation and dysmorphology. From a practical point of view, finding and treating an over-imposed inflammation could help limit damage in a hamartomatous syndrome.

Corresponding author: Siao-Pin Simon, Lecturer, MD, PhD; e-mail: siao_2003@yahoo.com

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25. Delayed interval delivery in twin pregnancy - case reports

Constantin-Cristian Vaduva, Carmen Constantinescu, Mihaela Tenovici, Alice Roxana Vaduva, Mihaela Niculescu, Damian Ditescu, Cristina Crenguta Albu, Dinu Florin Albu

The implementation of assisted reproduction has increased the incidence of multiple pregnancies. Prenatal death of one fetus in the second trimester of twin pregnancy confronts the obstetrician with a difficult problem with regard to the management of pregnancy. The scarcity of the condition and the absence of the large-scale studies make it difficult to advise the parents on the prognosis and optimal management. The unavoidable birth or death of one premature neonate has led to the aim of delayed interval delivery for the other twin. We present in this report two cases of twin pregnancies with delayed-interval delivery and favorable outcomes for the surviving twins. The twin pregnancies conceived by in vitro fertilization (IVF) in HitMed Medical Center, Craiova, Romania. In the first case, one fetus dismiss in utero at 20 weeks of gestation. The second fetus was successfully delivered by Caesarean section, at 36 weeks. In the second case, the first fetus was delivered at 22 weeks. To save the surviving fetus, ligation of the umbilical cord at the cervical level was performed. The second fetus was delivered at 31 weeks by Caesarean section, in good conditions. We describe our management of the cases and the deliveries and the neonatal outcomes. In multiple gestation, prolongation of pregnancy after preterm dismiss in utero or even after delivery of one fetus is feasible in a closely monitored environment.

Corresponding author: Mihaela Niculescu, Lecturer, MD, PhD; e-mail: ela07071@yahoo.com

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26. Visceral and tissular reactivity in acute heart failure due to supraventricular tachyarrhythmia in a young patient

Maria Cristina Bezna, Doina Carstea, Marinela Bezna, Octavian Istratoaie, Ionela Cristina Deliu, Petru Razvan Melinte

Observation of major pathological alterations in a young person involves etiological and clinical justifications, in order to properly assess, treat and control these conditions. The aim of this paper is to present severe, acute pathological lesions, installed in a young person, secondary to hypodiastolic heart failure, due to persistent supraventricular tachyarrhythmia, triggered by a post-traumatic external stimulus, with complete remission post-electrical conversion. Pathological and clinical modification are revealed, in a young person, shortly after a minor thoracic trauma, in the absence of traumatic injury but with high-frequency palpitations onset and progressive installation of vascular, visceral and interstitial stasis modifications, as well as of vascular and tissular hypoperfusion with reactive vasoconstriction. These clinical and paraclinical aspects were: stasis hepatomegaly with hepatojugular reflux, pulmonary congestion with stasis rales, peripheral edema, transudative polyserositis - pericarditis, hydrothorax, ascites, dilatation of inferior vena cava and suprahepatic veins, decrease of arterial blood pressure, tissue and cutaneous vasoconstriction. Anatomical and clinical aspects, with major alterations (Vth degree hepatomegaly, polyserositis, peripheral edema, tachyarrhythmic heart contractions, hypotension, pallor accentuated by vasoconstriction) acutely installed in a previously healthy young person, require a rapid lesions diagnosis and emergency treatment due to vital risk, control of acute heart failure manifestations remission and proper monitoring. Differential diagnosis was focused on determining possible aspects like: acute heart failure (of various etiology), internal post-traumatic lesions or hemorrhages, tuberculosis polyserositis, collagenosis, nephrotic syndrome, protein deficiencies, neoplasia with hepatic determinations, hematological diseases (lymphomas, leukemias), considered in young patients. Severe visceral, vascular and tissular pathological alterations were reactively induced in a young person, by stasis and hypoperfusion due to hypodiastolic heart failure caused by persistent supraventricular tachyarrhythmia triggered post-traumatic, on a proarrhythmic structural heart.

Corresponding author: Marinela Bezna, Associate Professor, MD, PhD; e-mail: mella_8873@yahoo.com

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27. Parotid sclerosing mucoepidermoid carcinoma: a case report and immunohistochemical study

Florin-Liviu Gherghina, Adrian Camen, Maria Cristina Munteanu, Claudiu Margaritescu, Calin-Gabriel Sarla

Here we report the case of a 63-year-old female with a parotid sclerosing mucoepidermoid carcinoma diagnosed and treated at the Department of Oral and Maxillofacial Surgery, Emergency County Hospital of Craiova, Romania. The clinical and imaging investigation revealed a parotid malignant tumor with central fluid-filled cystic formation. Histopathology found an intermediate grade sclerosing mucoepidermoid carcinoma that invaded the adjacent adipose and striated muscle tissues, but without perineural and lymphovascular invasion. The immunohistochemistry investigated mainly biomarkers involved in the induction of a local aggressive behavior. This case report describes a rare parotid sclerosing mucoepidermoid carcinoma with peculiar clinical and morphological characteristic features. The immunohistochemical study sustained its intermediate grade malignancy highlighting the prognostic value of some of the used biomarkers.

Corresponding author: Claudiu Margaritescu, Professor, MD, PhD; e-mail: c_margaritescu2000@yahoo.com

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28. Stillbirth in dichorionic twins discordant for major and minor anomaly, followed by asynchronous delivery - a rare occurrence. Case presentation

George Lucian Zorila, Marius Cristian Marinas, Maria Florea, Ciprian Laurentiu Patru, Roxana Cristina Dragusin, Razvan Grigoras Capitanescu, Marian Valentin Zorila, Roxana Eugenia Zavoi, Cristiana Eugenia Simionescu, Dominic Gabriel Iliescu, Stefania Tudorache

The single stillbirth long-term intrauterine retention in dichorionic twin pregnancy is rarely reported. Also, the birth of a fetus is followed in most cases by immediate expulsion of the second twin. We hereby present an unusual case of asynchronous delivery of dichorionic twins, associating discordance for major and minor anomaly. The intrauterine death of the twin A, presenting a large sacrococcygeal tumor, occurred in the second trimester. The deceased twin A was born at 29 weeks gestational age (GA). The twin B was extracted by Caesarean section at 31 weeks and had a good outcome. We performed a close follow-up of the high-risk pregnancy and we used tocolytic and antibiotic drugs for prolonging it. Corticoid therapy was administered for the lung maturation of the second twin. The expectant management in the single twin stillbirth dichorionic pregnancy and the asynchronous delivery had a significant impact on the newborn outcome.

Corresponding author: Marian Valentin Zorila, MD, PhD; e-mail: zorilavaly@yahoo.com.au

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29. Acute cellulitis as local reaction to orthopedic implant - case presentation

Olivera Lupescu, Mihail Nagea, Razvan Scurtu, Nicolae Marian Ciurea, Alexandru Lisias Dimitriu, Narcis Marcov, Gheorghe Ion Popescu, Simona Bondari

Due to increasing number of arthroplasties and osteosynthesis, foreign body reaction to implants is a major problem for orthopedic surgeons, since it is considered to be responsible for severe complications impairing the outcome of the treatment and requiring multiple surgery. Different mechanisms have been described as being involved, and research is focused on finding biomaterials with increased biocompatibility in order to minimize these complications. The clinical aspect of this reaction is usually dominated by chronic pain, with mild functional deficits, and the diagnosis results from excluding other causes of chronic pain, such as infection, osteoarthritis, peripheral neuropathies or angiopaties. The authors present a case with unusual clinical aspect, that of acute cellulitis, when early proper treatment, represented by implant removal, allowed healing without the onset of infection or other complications; histological evaluation confirmed the reaction to implant, thus concluding that surgical treatment when intolerance to implant is suspected is the only method to prevent future negative events.

Corresponding author: Nicolae Marian Ciurea, MD, PhD Student; e-mail: dr.ciureanicolae@gmail.com

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30. Smoking-associated nodular glomerulosclerosis, a rare renal pathology resembling diabetic nephropathy: case report

Andreea Gabriella Andronesi, Gener Ismail, Andreea-Catalina Fetecau, Mihaela Gherghiceanu, George Mitroi, Mihai Cristian Harza

Introduction: Smoking is an important risk factor not only for cardiovascular and pulmonary diseases, but also for the progression of chronic kidney disease of different etiologies. Nodular glomerulosclerosis is a renal pathology pattern, which was described in different kidney conditions, especially diabetic nephropathy. A very rare association among smoking, hypertension and nodular mesangial glomerulosclerosis has been recently described. Case presentation: In this paper, we present the case of a non-diabetic male patient referred to our Department for advanced chronic kidney disease and nephrotic syndrome. After excluding different causes of secondary nephrotic syndrome, a kidney biopsy was performed. The patient was diagnosed with smoking associated nodular glomerulosclerosis, with a histological aspect closely resembling diabetic nephropathy. A low protein and low salt diet was started, accompanied by smoking cessation, the administration of diuretics, of antiproteinuric treatment with angiotensin receptor blocker and antihypertensive therapy. Under this therapy, after six months, the patient evolution was good with a clear improvement of kidney function and important reduction of proteinuria. Discussion: We also present the possible factors that could be involved in the deleterious effects of smoking upon kidney structure endothelial dysfunction, angiogenesis, altered intrarenal hemodynamics, nervous sympathetic system, increased oxidative stress and, very important, the generation of advanced glycation end products, which are also implicated in the development of diabetic nephropathy. Conclusions: Although a rare condition, smoking associated nodular glomerulosclerosis is a diagnosis not to be missed when dealing with a heavy smoker patient, especially when hypertensive, and sometimes associating nephrotic syndrome and this diagnosis should be considered together with much more frequent causes of nephrotic syndrome.

Corresponding author: Andreea Gabriella Andronesi, MD; e-mail: andreea.andronesi@yahoo.com

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31. Vaginal epithelioid angiosarcoma: a rare case

Elvira Bratila, Oana-Maria Ionescu, Costin Berceanu, Ciprian-Andrei Coroleuca, Carmen Maria Ardeleanu, Claudia Mehedintu

Epithelioid angiosarcoma of the vagina is a rare variant, easily misdiagnosed as other epithelial neoplasms. On Hematoxylin-Eosin-stained sections, the pathologist encounters sheets of large, mildly to moderately pleomorphic epithelioid cells, with abundant eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. We report the case of a 22-year-old woman initially diagnosed with condiloma-like tumor of the left vaginal wall, which turned out positive at immunostaining for epithelioid angiosarcoma. In her case, after the failure of chemotherapy in controlling the relapse of the disease, the only treatment option was radical hysterectomy with bilateral salpingo-oophorectomy

Corresponding author: Costin Berceanu, University Lecturer, MD, PhD; e-mail: dr_berceanu@yahoo.com

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32. A case of Sweet s syndrome associated with uveitis in a young male with ulcerative colitis

Ligia-Ariana Bancu, Corina Ureche, Nicoleta-Maria Craciun, Dorin Marian

Sweet s syndrome is rare acute febrile neutrophilic dermatosis whose onset is either idiopathic or associated with other underlying conditions, such as infections, autoimmune diseases, pregnancy, use of certain medications, or malignancy. We report the case of a young male with known history of ulcerative colitis and abrupt onset of high fever, malaise, blurred vision and eruption of painful erythematous nodules and papules, localized on the head, neck, trunk and upper limbs. Ophthalmological examination established the diagnosis of anterior uveitis. Inflammatory markers were positive. Histological examination of skin lesions revealed a dense neutrophilic infiltrate of the dermis. Clinical, laboratory and histological findings were suggestive for the diagnosis of Sweet s syndrome and uveitis on a background of ulcerative colitis. Systemic and ophthalmic administration of corticotherapy leads to a prompt resolution of symptoms and inflammatory syndrome. The particularity of this case is the occurrence of two simultaneous extraintestinal manifestations in a young male with inflammatory bowel disease and colonic involvement. Although a relatively rare condition, Sweet s syndrome should be considered as a differential diagnosis in patients with acute onset of high fever and skin rash, as it may have notable internal involvement and can be easily treated.

Corresponding author: Corina Ureche, Lecturer, MD, PhD; e-mail: corina.ureche@gmail.com

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33. Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy in acromegalic patient with severe headache

Luminita-Nicoleta Cima, Simona Vasilica Fica, Alice Ioana Albu, Ioana Maria Lambrescu, Ioana-Smarandita Lacau, Bogdan Ovidiu Popescu, Mihaela Gherghiceanu, Corin Virgil Badiu, Carmen Gabriela Barbu

A 68-year-old female patient was admitted in our clinic with severe frontal bilateral headache, dizziness, depression and cognitive decline in the context of a previously diagnosed acromegaly. She also had high blood pressure, dyslipidemia, secondary diabetes mellitus. Acromegaly was caused by a growth hormone (GH) secreting-pituitary macroadenoma, so a transsphenoidal surgery was performed. The postoperative magnetic resonance imaging (MRI) scan revealed a 20/22/25 mm pituitary mass remnant and medical therapy with somatostatin analogues (SSAs) was started. After nine months of treatment with SSAs, she continued having severe headache, the blood pressure was well controlled, but GH secretion was only partially controlled with insulin-like growth factor-1 (IGF-1) level still above the normal value. The MRI scan showed the same pituitary tumor remnant with supra- and parasellar right extension and also multiple fronto-temporo-parietal subcortical lesions that could suggest in the clinical context cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). According to a pregenetic screening tool, the Pescini Scale, the patient had a 19 points score, which is highly suggestive for CADASIL, an inherited cerebrovascular disease due to mutations of the Notch3 gene at the chromosome locus 19p13. In the absence of genetic testing, an alternate way to prove small vessels disease, the skin biopsy, was performed. Electron microscopy showed granular osmiophilic material (GOM) surrounding the vascular smooth muscle cells on that are pathognomonic for the disease. Our report underscores the importance of repeated investigations even in patients with apparently obvious explanations of their condition since they may have multiple diseases with the same presenting clinical signs.

Corresponding author: Corin Virgil Badiu, Professor, MD, PhD; e-mail: badicrin@yahoo.co.uk

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34. Clinical and morphological considerations in one case with cervical cancer and right ureterohydronephrosis

Cristina Georgiana Ghib Para, Mircea Florin Sferdian, Voicu Dascau, Lucian Paiusan, Ioan Ioiart

We present the case of a 34-year-old female with cervical cancer and right ureterohydronephrosis. She was admitted to the Urology Clinic of the Emergency County Hospital of Arad, Romania, on November 11, 2015, after previously being diagnosed with stage IIIA cervical cancer in December 2014 and undergoing radio and chemotherapy and laparotomy for staging. At the moment of hospital admission, the patient suffered from fever and right lumbar pain, she was also diagnosed with grade IV right ureterohydronephrosis. The patient was operated at the Urology Clinic of Arad; the intervention involved a total hysterectomy with bilateral adnexectomy and a right obturatory necrectomy of the necrotic lymph nodes. However, the evolution was favorable. The purpose was to increase the patient s survival rate and increase the quality of her life by also applying one palliative method including a urethral stent. As a result, the patient s life was extended.

Corresponding author: Mircea Florin Sferdian, Lecturer, MD, PhD; e-mail: mirceasf@gmail.com

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35. Supernumerary fronto-orbital arteries arising from contralateral anterior cerebral artery associated with partially duplicated anterior communicating artery - case study and literature review

Alin Horatiu Nedelcu, Razvan Tudor Tepordei, Anca Sava, Cristinel Ionel Stan, Anda Maria Aignatoaei, Traian Taranu, Manuela Ursaru

The anatomical variations of the fronto-orbital artery are uncommon and rarely described in literature. During the dissection of a 64-year-old female formalized brain, we discovered a particular congenital abnormality regarding the arterial supply of the right fronto-orbital gyrus. We identified three arterial sources: a low caliber ipsilateral fronto-orbital artery that arises from the A2 segment of the right anterior cerebral artery and ends in the posterior part of the fronto-orbital gyrus, a large aberrant contralateral fronto-orbital artery that arises from the A2 segment of the left anterior cerebral artery, supplying most of the right fronto-orbital gyrus and a small accessory branch of the left anterior cerebral artery passing towards the contralateral fronto-orbital gyrus. These abnormalities are associated with a partially duplicated anterior communicating artery. This case shows a unique pattern of congenital brain vascular abnormalities that may have clinical and surgical implications.

Corresponding author: Anca Sava, Professor, MD, PhD; e-mail: dr.anca.sava.68@gmail.com

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36. Gallbladder carcinoma - a rare cause of pyloric-duodenal stenosis

Zizi Niculescu, Victoria Ulmeanu, Mihaela Maria Ghinea, Liliana Mocanu, Costin Niculescu, Mircea Grigorian

Pyloric duodenal stenosis is usually caused by pyloric, juxtapyloric or duodenal ulcer, or by postbulbar ulcer. Gallbladder cancer (GBC), duodenal diverticula, annular pancreas and superior mesenteric artery syndrome (Wilkie s syndrome) are rare causes of pyloric duodenal stenosis. The case of a 66-year-old female patient is presented. The patient was admitted to hospital presenting anorexia, repeated alimentary vomiting, epigastric pain, and weight loss. Objective clinical examination upon admission: clapotage a jeun is present, triggered by tapping the epigastric region. Laboratory tests reveal moderate anemia, hypokalemic alkalosis, increased levels of cholestatic enzymes and of tumor markers. Gastroendoscopy: Stomach presenting stasis fluid in large quantity. Deformed antropyloric region caused by extrinsic compression. Abdominal native magnetic resonance imaging (MRI) and with contrast medium: cholecyst lumen entirely obstructed with calculi; thickened wall, with heterogeneous gadolinophilia; gadolinophilic mass erasing the bordering limit in relation to the cholecyst wall and the colon hepatic angle, and leaving a print on the pyloric region. During surgery, upon opening the peritoneal cavity, a tumoral pericholecystic block was observed, including the pyloric-duodenal region and the transverse mesocolon. Histopathology tests of tissue samples showed adipose conjunctive tissue with invasive adenocarcinoma. Immunohistochemical tests [cytokeratin (CK) 7, CK17, CK19, CK20, CDX2, mucin (MUC) 1, MUC2, MUC5AC, MUC6, epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA)] were consistent with infiltrating neoplastic carcinoma, originating in the gallbladder epithelium. Gastrointestinal obstruction cases caused by gallbladder carcinoma are rare. The pyloric-duodenal region is more frequently affected, as compared to the small intestine or the colon.

Corresponding author: Zizi Niculescu, Professor, MD, PhD; e-mail: ziziniculescu@yahoo.co.uk

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37. Distinction between mesothelioma and lung adenocarcinoma based on immunohistochemistry in a patient with asbestos bodies in bronchoalveolar fluid - case report

Agripina Rascu, Eugenia Naghi, Marina-Ruxandra Otelea, Floarea Mimi Nitu, Oana-Cristina Arghir

Asbestos is a mineral-mined form the rocks, consisting in amosite (brown asbestos), crocidolite (blue asbestos) and/or chrysotile (white asbestos) used in many industries. Researches about the exposure to asbestos dust and asbestosis related diseases started almost a century ago. The first case report of fatal asbestosis disease was published in 1906, in England, by Dr. Hubert Montague Murray. A decade after, asbestos curious bodies were firstly described in the lung tissue by Cooke (1926) and McDonald (1927). Occupational exposure to asbestos is now regulated in Romania, but past exposure is still a cause of asbestosis-related diseases (ARDs), including lung cancer. A peculiar association between a lung adenocarcinoma, a previously healed pulmonary tuberculosis (PTB) disease, is reported in a 61-year-old nonsmoker white man, a former factory worker with 29 years of occupational exposure history to cement and asbestos fibers. The positive diagnosis of asbestos exposure was facilitated by asbestos bodies determined in bronchoalveolar lavage fluid. The main purpose of this case report is to describe the development of a right pleural effusion which was not revelatory for a mesothelioma but for an adenocarcinoma of the lung. An accurate morphologic and immunohistochemistry assessment of a pleural biopsy sample excluded mesothelioma and was crucial in the positive diagnosis of adenocarcinoma. In conclusion, unilateral paraneoplastic pleural effusion in a nonsmoker male with occupational exposure to asbestosis fibers was suggestive for adenocarcinoma related asbestosis of the lung. Lung cancer and malignant pleural exudate developed after a long latency cumulative retention time of asbestos fibers.

Corresponding author: Floarea Mimi Nitu, Professor, MD, PhD; e-mail: dr_nitumimi@yahoo.com

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