Vol. 58 No. 4, October-December 2017

1. Tau protein in neurodegenerative diseases - a review

Denisa Floriana Vasilica Pirscoveanu, Ionica Pirici, Valerica Tudorica, Tudor-Adrian Balseanu, Valeria-Carmen Albu, Simona Bondari, Ana-Maria Bumbea, Mircea Pirscoveanu

The study of rare, inherited forms of different diseases resulted in the discovery of gene defects that cause inherited variants of the respective diseases. The defective genes were found to encode major molecular players leading to the neuropathological lesions or factors that characterize these diseases. The exact role of the tau protein in the neurodegenerative process is still under debate. It is very important to understand the normal biological roles of tau and the specific events that induce tau to become neurotoxic. Tau is the major microtubule-associated protein (MAP) of a mature neuron. The other neuronal MAPs are MAP1 and MAP2. These three MAPs perform similar function, promoting assembly and stability of microtubules. Tau protein was isolated as a microtubule-associated factor in the porcine brain. It was isolated as a protein that co-purified with tubulin and had the ability to promote microtubule assembly in vitro. Normal adult human brain tau contains 2-3 moles phosphate/mole of tau protein. Hyperphosphorylation of tau depress this biological activity of tau. Almost 80 diseases caused by missense mutations and intronic mutations in the tau gene have been found in familial cases of frontotemporal dementia (FTD). In Alzheimer s disease (AD), there are intraneuronal neurofibrillary tangles composed of the microtubule-associated protein tau (MAPT). In other neurodegenerative diseases, there are similar deposits of tau, in the absence of extracellular deposits (progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, etc.). Tau pathology is also often seen in some forms of Parkinson s disease (PD) and prion diseases. In genetic forms of FTD, mutations in tau implicate abnormal tau as the initiation of neurodegeneration. In FTD, there are deposits especially in temporal and frontal lobes, regions that are very important for behavior and executive function. It is critical to understand how tau becomes pathogenic, in order to consider developing any strategies for treatment.

Corresponding author: Ana-Maria Bumbea, Teaching Assistant, MD, PhD; e-mail:

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2. The importance of immunocytochemistry in the detection of high-grade cervical lesions

Adrian Claudiu Ratiu, Cristina-Anamaria Secosan, Oana Balint, Ioan Sas, Dorin Grigoras, Razvan-Stefan Ilina, Adelina Maria Jianu, Andrei Gheorghe Marius Motoc, Laurentiu Cornel Pirtea

Despite the implementation of various screening programs in many countries, cervical cancer continues to be a major health problem. Cervical cytology is the most used screening method, but human papillomavirus (HPV) genotyping, alone or in combination with cytology, has gained ground during the last years. Still, one of the major limitations of HPV-genotyping is the low specificity of HPV as a screening method in young women that are HPV-positive, but with no potential for future disease. Obviously, there is a need for a better screening algorithm. The ideal screening test for cervical high-grade lesions should detect the effect of high-risk (HR)-HPV infection after cell transformation, but not before, and should accurately identify the cases that are more likely to experience disease progression to neoplasia. Solid data regarding the benefit of immunocytochemistry in the evaluation of the patients with modified cervical cytology have been published recently. The use of the dual staining with p16INK4a and Ki-67 could increase specificity of the method for the detection of atypical cells and may perform better in predicting the risk of high-grade dysplasia in the near future.

Corresponding author: Cristina-Anamaria Secosan, MD, PhD; e-mail:

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3. Clinical and pathological features of splenic metastasis from cervical squamous cell carcinoma

Madalina Lucia Marcu, Adrian Neacsu, Claudia Stoica, Nicolae Bacalbasa, Andreea Contolenco, Eugen Radu

Isolated splenic metastases from squamous cell carcinoma (SCC) of the cervix are rare, with few cases reported in the literature. We review here the main clinical and pathological findings in these patients, with emphasis on histopathological features. Because they are so rare, complex follow-up protocols for patients diagnosed with cervical SCC should exist because, if detected and treated, solitary splenic metastases seem to have a better prognosis than splenic metastases as part of a disseminated disease.

Corresponding author: Adrian Neacsu, Associate Professor, MD, PhD; e-mail:

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4. Neurobiological arguments for a pathogenic multifactorial disconnective model of cognitive disorders from Alzheimer s disease in elderly people

Ileana Marinescu, Virgil Radu Enatescu, Stefan Mugurel Ghelase, Dragos Marinescu

Incidence of Alzheimer s disease (AD) in people over 75 years is much higher, and the progression of cognitive deficit become faster, leading to a decrease of quality of life for patients and their families. In this context, it is proposed a multifactorial pathogenic model of disconnected cognitive circuits, which is combined with genetic and vascular-cerebral vulnerability elements, allowing an aggressive progression of neurodegenerative factors, favoring onset of dementia. Data from research studies on animal model (rat) highlighted central role of cerebral cholinergic deficit (which is amplified by cerebral ischemia) on the background of apolipoprotein E4 (ApoE4) genotype, favoring multifactorial disconnected mechanisms, by excess of beta-amyloid (beta-A) or increase of vascular dysfunction. Depressive disorder, social stress and traumatic brain injury are favoring the excess in production of beta-A. Hippocampal structure disconnects the cognitive circuits, and from a neuropsychological point of view can be many patterns, which are correlated with neuroimaging (hippocampal atrophy, cerebral siderosis, white matter hyperintensity, ventriculomegaly) or biological (hyperhomocysteinemia) factors. Identifying the pathogenic model of multifactorial disconnectivity in the rapid evolution of cognitive deficit in patients with AD may create the premises for an early diagnosis and treatment, based on the biological, neuropsychological and clinical elements.

Corresponding author: : Stefan Mugurel Ghelase, Professor, MD, PhD; e-mail:

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5. Preselection of EGFR mutations in non-small-cell lung cancer patients by immunohistochemistry: comparison with DNA-sequencing, EGFR wild-type expression, gene copy number gain and clinicopathological data

Rania Gaber, Iris Watermann, Christian Kugler, Ekkehard Vollmer, Sven Perner, Martin Reck, Torsten Goldmann

Targeting epidermal growth factor receptor (EGFR) in patients with non-small-cell lung cancer (NSCLC) having EGFR mutations is associated with an improved overall survival. The aim of this study is to verify, if EGFR mutations detected by immunohistochemistry (IHC) is a convincing way to preselect patients for DNA-sequencing and to figure out, the statistical association between EGFR mutation, wild-type EGFR overexpression, gene copy number gain, which are the main factors inducing EGFR tumorigenic activity and the clinicopathological data. Two hundred sixteen tumor tissue samples of primarily chemotherapeutic naïve NSCLC patients were analyzed for EGFR mutations E746-A750del and L858R and correlated with DNA-sequencing. Two hundred six of which were assessed by IHC, using 6B6 and 43B2 specific antibodies followed by DNA-sequencing of positive cases and 10 already genotyped tumor tissues were also included to investigate debugging accuracy of IHC. In addition, EGFR wild-type overexpression was IHC evaluated and EGFR gene copy number determination was performed by fluorescence in situ hybridization (FISH). Forty-one/206 (19.9%) cases were positive for mutated EGFR by IHC. Eight of them had EGFR mutations of exons 18-21 by DNA-sequencing. Hit rate of 10 already genotyped NSCLC mutated cases was 90% by IHC. Positive association was found between EGFR mutations determined by IHC and both EGFR overexpression and increased gene copy number (p=0.002 and p<0.001, respectively). Additionally, positive association was detected between EGFR mutations, high tumor grade and clinical stage (p<0.001). IHC staining with mutation specific antibodies was demonstrated as a possible useful screening test to preselect patients for DNA-sequencing.

Corresponding author: Torsten Goldmann, Professor, Dr. rer. nat., Principal Investigator; e-mail:

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6. Study on cognitive decline in patients diagnosed with brain tumors

Simona Bondari, Dan Bondari, Mircea Pirscoveanu, Dan-Vasile Morosanu, Anca-Emanuela Musetescu, Valerica Tudorica, Denisa Floriana Vasilica Pirscoveanu

Aim: The purpose of our study was to assess the cognitive performance in patients with primitive brain tumors and to analyze the cognitive status of these patients, correlated with histological type of brain tumors. Patients, Materials and Methods: The study enrolled 52 patients diagnosed with primitive brain tumors, hospitalized in Neuropsychiatry Hospital of Craiova, Romania, from December 2013 to December 2015. According to the histological type of tumors, the patients were classified into three groups: Group A included 22 patients with meningioma, Group B composed of 16 patients diagnosed with glioblastoma, and Group C including 14 patients diagnosed with diffuse astrocytoma. Neurological examination, neuroimaging assessment [computed tomography (CT) or magnetic resonance imaging (MRI) for skulls] to diagnose primitive brain tumors, then the confirmation of clinical and histopathological diagnoses were performed for these patients. For cognitive assessment performed before surgery, Montreal Cognitive Assessment (MoCA) and Cambridge Cognitive Examination (CAMCOG) scales were used. The results were statistically analyzed using the Student s t-test; p-values less than 0.05 were considered statistically significant. Results: In terms of age, we did not observe statistically significant differences between the three groups of patients. The group of patients with diffuse astrocytoma presented a higher educational level compared to patients with glioblastoma or meningioma. MoCA score obtained in glioblastoma group was 21.7 points, while in the group of patients with diffuse astrocytoma was 23.5 points, and in the group of patients with meningioma 24.2 points. The cognitive assessment using CAMCOG scale led to the following results: group of patients diagnosed with glioblastoma showed an average score of 83.5 points, the diffuse astrocytoma group had an average score of 88.9 points and the group with meningioma an average score of 90.1 points. Conclusions: Patients diagnosed with glioblastoma showed a statistically significant cognitive decline in comparison to patients diagnosed with diffuse astrocytoma (p<0.05). We did not notice statistically significant differences in the cognitive decline of patients with meningioma compared to those diagnosed with diffuse astrocytoma (p>0.05).

Corresponding author: Mircea Pirscoveanu, University Assistant, MD, PhD; e-mail:

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7. Biomechanical and morphological peculiarities of the rectum in patients with obstructed defecation syndrome

Ints Brunenieks, Katrina Pekarska, Vladimir Kasyanov, Valerija Groma

The morphological and biomechanical peculiarities of the rectum observed in obstructed defecation syndrome (ODS) are not completely understood. The biomechanical properties and morphological features of the rectum in patients with ODS in correlation with the status of the enteric nervous system (ENS) were evaluated. Uniaxial tensile tests on the rectum samples of patients with ODS and controls were performed; collagenous constituents were assessed by Reticulin and Masson s trichrome stainings; the expressions of alpha-smooth muscle actin (alpha-SMA), S100 and CD117 labeling of interstitial cells of Cajal (ICCs) were investigated by immunohistochemistry. In both groups, the ultimate stress in the posterior rectal wall was statistically significantly higher compared to the anterior one. The ultimate strain was higher in ODS compared to controls. The tangential modulus of elasticity was significantly higher in the control group than in the ODS one, both in the anterior and posterior walls. A significantly higher density of collagen demonstrated throughout the wall was evidenced in controls compared to ODS. The mucosal muscular compartment was significantly thicker but more disorganized in the patients group. The enteric S100-positive glial cells were significantly reduced in number in the anterior wall, but elevated in the posterior wall of the rectum in ODS simultaneously demonstrating the higher numbers of ICCs within the entire muscular layer and myenteric. The biomechanical and morphological results show that the rectal wall in patients with ODS is more deformable and less rigid compared to controls. The results of biomechanical properties and morphological changes in the human rectum are essential when choosing the method of ODS treatment.

Corresponding author: Vladimir Kasyanov, Professor, PhD,; e-mail:

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8. Spatiotemporal expression of extracellular matrix components during the chondrogenic and osteogenic phases of bone healing

Moyses Messias Souza de Sant Anna, Luiz Alberto Batista, Thais Cristina Mendes da Silva, Liszt Palmeira Oliveira, Jorge Jose de Carvalho

In this study, we investigated the cascade of events involved in the early phases of bone healing in rats, especially the transition from chondrogenesis to osteogenesis, which involves cellular and extracellular matrix (ECM) components. We used a standardized closed tibial fracture model in Wistar rats, which was divided into nine groups of five animals each, and the fracture area was evaluated at 0, 12, 24, 48, 72, 96, 144, 192, and 240 hours post-injury. Histological, histochemical, immunohistochemical and morphometric techniques were used to evaluate the proliferating cell nuclear antigen (PCNA), transforming growth factor-beta (TGF-beta), vascular endothelial growth factor (VEGF), type I procollagen (procoll-I), type I collagen (coll-I), and type II collagen (coll-II) expression at every time point. TGF-beta expression peaked after 144 hours, in the initial chondrogenic phase. VEGF expression reached the first peak at 96-144 hours post-injury, in the initial chondrogenic phase and the second peak at 240 hours, in the osteogenic phase. Except at 48 hours, PCNA expression increased gradually from 12 hours and peaked at 96 hours in the prechondrogenic phase, and then decreased gradually until 240 hours in the osteogenic phase. Total collagen (T-coll) and coll-II reached an expression peak at 144 hours, in the chondrogenic phase. No differences were observed between their expression from 12 hours to 72 hours and at 240 hours post-injury. The results suggest that spatiotemporal expression of ECM components during the chondrogenic and osteogenic phases of bone healing depends on several combined and orchestrated factors. A better understanding of the coordinated participation of cells and ECM components in the early bone healing process may provide new insights into the etiology of abnormal or delayed fracture healing.

Corresponding author: Moyses Messias Souza de Sant Anna, MSc, PhD; e-mail:

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9. MRI differential diagnosis: bone metastases versus bone lesions due to malignant hemopathies

Ana Magdalena Bratu, Victor Paul Raica, Iulia Alecsandra Salcianu, Constantin Zaharia, Valeriu Bogdan Popa, Anca Roxana Lupu, Victorita Stefanescu, Camelia-Marioara Dobrea, Gheorghe Iana, Andreea Nicoleta Marinescu

Bone determinations are usually the first sign of disseminated cancers, whether is a hematological malignancy or other type of neoplasia. The aim of this paper is the possibility of differentiating the bone lesions from hematological malignancies by other malignancies that give bone metastases for the purpose to guide the clinician concerning causality of bone lesions. The research involved a retrospective study, which included 309 cases that were investigated by magnetic resonance imaging (MRI) at a segment of the spine, between 2010 and 2014, from which 137 were diagnosed with a form of hematological neoplasia, and the remaining had another form of cancer. Imaging aspect differs in these two study groups. Bone determinations due to malignant hemopathies (MH) were in general hypointense on T1-weighted sequences, iso- or hyperintense on T2-weighted sequences. On the other hand, bone metastases were hypo- or isointense on T1-weighted sequences, and had no specific signal intensity on T2-weighted sequences. In post-contrast images, all lesions showed contrast enhancement, with some differences. In terms of imagistic aspect, there are certain characteristics that can make a clear differentiation between bone determinations due to MH from the bone metastases, and some are found in the majority of the cases studied.

Corresponding author: Iulia Alecsandra Salcianu, MD, PhD; e-mail:

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10. Comparison of pathology, blood gas and biomarkers between two rat models of acute lung injury

Yuan-Dong Hu, Ling Jiang, Liu-Lin Xiong, Yue Hu, Qing-Jie Xia, Ting-Hua Wang

An ideal animal model to explore pathogenesis and prevention of acute lung injury (ALI) is essential. The present study aims to compare the difference in pathology, blood gas values and biomarkers of two acute lung injury rat models at different time intervals. In the experiment, rats were randomly divided into three groups: lipopolysaccharide (LPS) group, oleic acid (OA) group and control group. Changes of pathology, blood gas values and blood-air barrier biomarkers were analyzed at 15 minutes, 6 hours, 12 hours and 24 hours after injection. The results showed that the two models exhibited different features. Compared with the LPS rats, OA rats exhibited significantly severe pathological changes, lower arterial oxygen partial pressure (PaO2) value and higher level of injury biomarkers. However, LPS rats boasted greater lactic acid (LAC) level and more severe acidosis than OA rats. This study suggests that LPS-induced model has greater value in researches on microcirculation dysfunction and sepsis resulting from ALI, while OA-induced model has greater repeatability in area of gas exchanging after ALI. These events may provide a new theoretical evidence for the model establishment of ALI.

Corresponding author: Ting-Hua Wang, Professor, MD, PhD; e-mail:

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11. Comparing the antifibrotic effect on the liver of Telmisartan and Pentoxifylline, in a Wistar rat experimental model

Floriana Elvira Ionica, Laurentiu Mogoanta, Simona Negres, Ludovic Everard Bejenaru, Oana Mariana Cristea, Oana Badea, Cornelia Bejenaru

Chronic liver diseases are characterized by higher or lower changes of the liver lobe architecture (parenchymatous and vacuolar), the accumulation of inflammatory and collagen infiltrates, mainly in the Kiernan spaces and a progressive evolution to liver cirrhosis. Despite the progresses made in knowing the mechanisms of liver fibrosis and the development of some antiviral drugs with a high potential, that can induce fibrosis regression, there still continues to exist the need for a specific antifibrotic treatment. In our study, we used four groups of Wistar rats: a reference group and three groups that received 40% carbon tetrachloride (CCl4), intraperitoneally, twice a week, for four weeks; after one week since starting the administration of CCl4, one of the three groups received, through oral gavage, Telmisartan (TS) 8 mg/kg, and another received Pentoxifylline (PTX) 20 mg/kg, dissolved in saline solution, for four weeks. The antifibrotic action of the two drugs was analyzed by evaluating the histopathological and immunohistochemical changes of hepatocytes, hepatic stellate cells (Ito cells) and macrophages (Kupffer cells). The study highlighted that in the group treated with TS, the process of fibrillogenesis was significantly reduced, in comparison to the group treated with PTX and with the reference group.

Corresponding author: Ludovic Everard Bejenaru, Associate Professor, Biol, Pharm, PhD; e-mail:

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12. Increased osteopontin expression and mitochondrial swelling in 3-nitropropionic acid-injured rat brains

Hong-Lim Kim, Byung-Joon Chang, Sung Min Nam, Sang-Soep Nahm, Jong-Hwan Lee

Osteopontin (OPN) is involved in the regulation of calcium precipitation in the brain pathology including ischemia. A 3-Nitropropionic acid (3NP) irreversibly inhibits mitochondrial complex II in the electron transport chain, with subsequent loss of transmembrane potential and calcium entry into the mitochondria. The present study examined the 3NP-induced calcium elevation in mitochondria and OPN expression in the 3NP-lesioned striatum. Rats were subcutaneously injected 3NP (15 mg/kg) every other day for six weeks. Histological analysis, including the Hematoxylin-Eosin, Nissl, and Alizarin Red S stainings, was performed to examine the neurotoxic effects of 3NP. The expression of OPN in the striatum of 3NP-treated rats was investigated with immunohistochemistry and immunoelectron microscopy. In the striatal lesions, extensive loss of neurons and white matter bundles was detected. OPN was mainly detected in the penumbra region of the 3NP lesion. Scattered OPN expression was colocalized in the striatal neurons. After Alizarin Red S staining, the increase of calcium deposition was detected in the striatal lesions. In the electron microscopic analysis, the localization of OPN was clearly observed in the ultrastructure of mitochondria by immunoperoxidase and immunogold-silver staining techniques. Taken together, present findings suggest that calcium-induced mitochondrial swelling is highly associated with OPN expression. Thus, striatal calcium accumulation may be derived from 3NP-induced alteration in mitochondrial calcium homeostasis and pathologically associated with the induction of OPN protein.

Corresponding author: Jong-Hwan Lee, Professor, DVM, PhD; e-mail:

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13. The tyrosine kinase inhibitors effects on metastatic tumor graft in the chick chorioallantoic membrane assay

Alexandru Ciolofan, Octavian Marius Cretu, Stelian Stefanita Mogoanta, Eduard Mihai Ciuca

Background: Due to its heterogeneous nature, pancreatic cancer has a higher incidence and a clinical treatment failure. In this study, we present the effects of Avastin, Rapamycin and their combination on the pancreatic liver metastatic human tumor graft in the chick chorioallantoic membrane (CAM) assay. Materials and Methods: We conducted this study with 33 fertilized chicken eggs, incubated at 37 degrees C, divided into three working groups: control (three eggs), first (10 eggs), second (10 eggs), and third group (10 eggs). A cell suspensions derived from human liver metastasis of pancreatic tumor were implanted on the CAM, in the ring. First group was treated with 2 micro-L Avastin (Bevacizumab 25 mg/mL), the second with Rapamycin and the third with Avastin and Rapamycin combination on days 10, 12, 14 of incubation. The immunohistochemical techniques using vascular endothelial growth factor A (VEGFA), CD34, podoplanin, platelet-derived growth factor subunit A (PDGFA) and epidermal growth factor receptor (EGFR) as primaries antibodies were performed on metastatic tumor and metastatic tumor graft. Results: Our results showed that the unique treatment with Avastin gave rise to metastases on CAM xenograft, due likely to inflammatory infiltrate and vascular remodeling. The lowest immunoexpression of CD34, podoplanin, PDGFA, EGFR has been noticed in the Rapamycin-treated group without important differences correlated to dosage and time. In the third group, decreased value was found for PDGFA only. The periphery of the tumor graft malignant cells intensely expressed VEGFA, podoplanin and EGFR. Conclusions: The inhibitory therapy with mechanistic target of Rapamycin (mTOR) and Avastin may favor the epithelial to mesenchymal transition by podoplanin and phosphatase and tensin homolog (PTEN) pathways in liver metastasis pancreatic graft to CAM.

Corresponding author: Octavian Marius Cretu, Professor, MD, PhD; e-mail:

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14. Mucosal CCR1 gene expression as a marker of molecular activity in Crohn s disease: preliminary data

Maria Dobre, Teodora Ecaterina Manuc, Elena Milanesi, Iancu Emil Plesea, Eugen Nicolae Tieranu, Caterina Popa, Mircea Manuc, Carmen Monica Preda, Ioana Tieranu, Mihai Mircea Diculescu, Elena Mirela Ionescu, Gabriel Becheanu

Aim: A series of mechanisms of immune response, inflammation and apoptosis have been demonstrated to contribute to the appearance and evolution of Crohn s disease (CD) through the overexpression of several cytokines and chemokines in a susceptible host. The aim of this study was to identify the differences in gene expression profiles analyzing a panel of candidate genes in the mucosa from patients with active CD (CD-A), patients in remission (CD-R), and normal controls. Patients, Materials and Methods: Nine individuals were enrolled in the study: six CD patients (three with active lesions, three with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression levels of 84 genes previously associated with CD were evaluated by polymerase chain reaction (PCR) array. Results: Ten genes out of 84 were found significantly differentially expressed in CD-A (CCL11, CCL25, DEFA5, GCG, IL17A, LCN2, REG1A, STAT3, MUC1, CCR1) and eight genes in CD-R (CASP1, IL23A, STAT1, STAT3, TNF, CCR1, CCL5, and HSP90B1) when compared to controls. A quantitative gene expression analysis revealed that CCR1 gene was more expressed in CD-A than in CD-R. Conclusions: Our data suggest that CCR1 gene may be a putative marker of molecular activity of Crohn s disease. Following these preliminary data, a confirmation in larger cohort studies could represent a useful method in order to identify new therapeutic targets.

Corresponding author: Teodora Ecaterina Manuc, MD, PhD Candidate; e-mail:

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15. The immunoexpression of EGFR, HER2 and HER3 in malignant serous ovarian tumors

Andreea-Elena Cirstea, Alex Emilian Stepan, Claudiu Margaritescu, Roxana Eugenia Zavoi, Daniel Alin Olimid, Cristiana Eugenia Simionescu

The expression of epidermal growth factor (EGF) receptors is common in human carcinomas and the proteins are used as therapeutics targets. In this study, we analyzed the immunoexpression of EGFR, HER2 (EGFR2) and HER3 (EGFR3) in 41 cases of serous borderline ovarian tumors and carcinomas, in relation to the degree of differentiation and tumor stage. The quantification of the results was done using the final staining score (FSS), which took into account the number of labeled cells and the intensity of immunoreactions. For all the receptors, the FSS values corresponding to the high-grade serous carcinomas were significantly superior compared with low-grade carcinomas and borderline tumors. Also, the FSS values associated with advanced stages ovarian tumors were significantly superior compared to those in the initial stages. In this study, we found positive linear correlations between the values associated with the expression of EGF receptors. The relation of EGFR, HER2 and HER3 immunoexpression with the lesion subtype, tumor grade and stage, designates the EGF receptors system as possible therapeutic target in ovarian serous tumors.

Corresponding author: Alex Emilian Stepan, Lecturer, MD, PhD; e-mail:

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16. CDX2 expression can predict response to neoadjuvant therapy in gastric carcinoma

Maria Jesus Fernandez Acenero, Maria Luisa Sanchez de Molina, Ana Caso, Peter Vorwald, Damian Garcia Olmo, Jorge Palomar, Lourdes Estrada, Cristina Diaz del Arco

Purpose: Caudal-related homeobox transcription factor 2 (CDX2) has recently been proposed as a prognostic factor for gastric carcinoma. However and to the best of our knowledge, no previous report has analyzed CDX2 expression in patients with gastric adenocarcinoma receiving neoadjuvant therapy (NAT). Patients, Materials and Methods: This is a retrospective cohort study to analyze the potential role of CDX2 expression to predict response to NAT and prognosis. This study has enrolled 57 patients receiving chemotherapy for locally advanced gastric carcinoma. Results: 59.6% of the patients were men; mean age was 64.96 years. Only 8% of the patients showed a complete response to therapy, 10% had grade 1, 28% grade 2, and 54% grade 3 regression, respectively, according to modified Ryan s criteria. On follow-up, 38.6% of the patients showed recurrence of disease (50% distant metastasis) and 28.1% eventually died of it. Twenty-three (40.4%) patients showed intense CDX2 expression. We found a statistically significant association between CDX2 expression and poor regression with NAT, but we found no association with outcome. Discussion: Our study indicates that CDX2 expression can predict lack of response to NAT. Our results have not confirmed the association with prognosis shown in previous reports. Conclusions: Despite these preliminary results, furthermore studies are necessary to define the potential use of CDX2 in gastric carcinoma.

Corresponding author: Maria Jesus Fernandez Acenero, MD, PhD; e-mail:

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17. Improved diagnosis and long-term recurrence rate reduction for non-muscle-invasive bladder cancer patients undergoing fluorescent hexylaminolevulinate photodynamic diagnosis

Petru Octavian Dragoescu, Stefania Tudorache, Andrei Ioan Drocas, George Mitroi, Andrei Panus, Nicoleta Alice Marilena Dragoescu, Cristian Mesina, Cosmin Daniel Mititelu, Andreea Doriana Stanculescu, Guleed Mohamed, Paul Ioan Tomescu

Background: Bladder cancer (BC) currently accounts for 5% of all malignancies and the most common tumor of the urinary tract. Diagnosis of bladder cancer is based on urine cytology and white-light cystoscopy (WLC) performed for patients with suspected bladder mass and/or hematuria. Recent studies suggest that using the fluorescence photodynamic diagnosis (PDD) significantly improves diagnostic sensitivity with a positive influence upon the recurrence rate of bladder cancer. Objective: To evaluate the diagnostic efficiency and long-term influence upon the tumor recurrence rate for patients with non-muscle-invasive bladder cancer (NMIBC) undergoing hexaminolevulinate PDD compared to standard WLC. Patients, Materials and Methods: Between 2009 and 2011, 113 primary NMIBC patients were enrolled in our prospective study and randomized in two parallel groups: 57 patients in the study group (PDD) and 56 patients in the control group (WLC). All patients had primary Ta/T1 NMIBC with good life expectancy and no significant bladder outlet obstruction [postvoid residual urine volume (PVR) <100 mL]. Results: Fluorescence cystoscopy examination identified 26.3% more tumors than the conventional examination (p=0.034) in the PDD group. Tumor recurrence rate analysis proved a significant reduction by up to 20% after five years of follow-up by using PDD [hazard ratio (HR) 0.566, 95% confidence interval (CI) 0.343-0.936; p=0.0267]. Conclusions: The use of PDD for patients with NMIBC results in a significant 26% diagnostic sensitivity improvement as well as superior patient prognosis and quality of life following conservative treatment by reducing the tumor recurrence rate with up to 20% after five years of follow-up.

Corresponding author: Stefania Tudorache, Associate Professor, MD, PhD, Senior Obstetrics and Gynecology Specialist; e-mail:

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18. Glutathione S-transferase (GSTM1, GSTT1) gene polymorphisms, maternal gestational weight gain, bioimpedance factors and their relationship with birth weight: a cross-sectional study in Romanian mothers and their newborns

Claudiu Marginean, Claudia Violeta Banescu, Cristina Oana Marginean, Florin Tripon, Lorena Elena Melit, Mihaela Iancu

Introduction: The aim of this study was to assess the relationship between mother-child GSTM1, GSTT1 gene polymorphisms, maternal weight gain, maternal bioimpedance parameters and newborn s weight, in order to identify the factors that influence birth weight. Patients, Materials and Methods: We performed a cross-sectional study on 405 mothers and their newborns, evaluated in an Obstetrics and Gynecology Tertiary Hospital from Romania. Results: Newborns whose mothers had the null genotype of GSTT1 gene polymorphism were more likely to gain a birth weight of >3 kg, compared to newborns whose mothers had the T1 genotype (odds ratio - OR: 2.14, 95% confidence interval - CI: [1.03; 4.44]). Also, the null genotype of GSTM1 gene polymorphism in both mothers and newborns was associated with a higher birth weight. Gestational weight gain was positively associated with newborn s birth weight (p<0.001). The increased mother s fat mass (%) and basal metabolism rate were also independent factors for a birth weight of more than 3 kg (p=0.006 and p=0.037). The null genotype of GSTT1 gene polymorphism in mothers and the null genotype of GSTM1 in mothers and newborns had a positive effect on birth weight. Also, increased maternal fat mass and basal metabolism rate were associated with increased birth weight. Conclusions: We conclude that maternal GSTM1/GSTT1 gene polymorphisms present an impact on birth weight, being involved in the neonatal nutritional status. The clinical relevance of our study is sustained by the importance of identifying the factors that influence birth weight, which can be triggers for childhood obesity.

Corresponding author: Claudia Violeta Banescu, Professor, MD, PhD; e-mail:

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19. Modified Whipple-Child pancreaticoduodenectomy with anastomosis on jejunal loop in continuity. Presentation of surgical technique and preliminary observations on 45 patients

Octavian Marius Cretu, Emil Florin Hut, Radu Gheorghe Dan, Laurentiu Vasile Sima, Ciprian Iulian Alexandru Blidisel, Daniel Florin Lighezan, Mihnea Munteanu, Iulia Maria Ratiu

Introduction: Cephalic pancreaticoduodenectomy (CPD) is the only current treatment method that can provide long-term survival in patients with periampullary tumors. Case presentation: This study is a prospective study conducted between 2010 and 2016 in Hepato-Biliary-Pancreatic Center of Victor Babes University of Medicine and Pharmacy, Timisoara, Romania, where 57 modified Whipple-Child CPDs with anastomoses on jejunal loop in continuity were performed, in patients with periampullary tumors. Twelve patients, who had undergone prior biliodigestive derivations or biliary drainage using endoscopic retrograde cholangio-pancreatography (ERCP), with stenting of the common bile duct, were excluded from the study. In 45 patients with modified Whipple-Child CPDs with anastomosis on jejunal loop in continuity, which were included in the study, overall morbidity rate was 22.22%. Postoperative mortality (within 30 days after the surgery) was 6.66% and six months and one year survival rates, excluding the four patients who died postoperatively, were 91.11% and 80%, respectively, with a median survival of 32 months. The mean operative time was 300 minutes, ranging between 240 and 390 minutes. Conclusions: Modified Whipple-Child CPD with anastomoses on jejunal loop in continuity seems to be a therapeutic method promising a decreased overall morbidity rate and a good quality of life and offering a distant survival rate, which is consistent, so far, with data reported in the literature.

Corresponding author: Emil Florin Hut, Assistant Professor, MD, PhD; e-mail:

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20. Gene expression profile of endoscopically active and inactive ulcerative colitis: preliminary data

Cristian George Tieranu, Maria Dobre, Teodora Ecaterina Manuc, Elena Milanesi, Iancu Emil Plesea, Caterina Popa, Mircea Manuc, Ioana Tieranu, Carmen Monica Preda, Mihai Mircea Diculescu, Elena Mirela Ionescu, Gabriel Becheanu

Aim: Multiple cytokines and chemokines related to immune response, apoptosis and inflammation have been identified as molecules implicated in ulcerative colitis (UC) pathogenesis. The aim of this study was to identify the differences at gene expression level of a panel of candidate genes in mucosa from patients with active UC (UCA), patients in remission (UCR), and normal controls. Patients, Materials and Methods: Eleven individuals were enrolled in the study: eight UC patients (four with active lesions, four with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression profile was evaluated by polymerase chain reaction (PCR) array, investigating 84 genes implicated in apoptosis, inflammation, immune response, cellular adhesion, tissue remodeling and mucous secretion. Results: Seventeen and three genes out of 84 were found significantly differentially expressed in UCA and UCR compared to controls, respectively. In particular, REG1A and CHI3L1 genes reported an up-regulation in UCA with a fold difference above 200. In UCR patients, the levels of CASP1, LYZ and ISG15 were different compared to controls. However, since a significant up-regulation of both CASP1 and LYZ was observed also in the UCA group, only ISG15 levels remained associated to the remission state. Conclusions: ISG15, that plays a key role in the innate immune response, seemed to be specifically associated to the UC remission state. These preliminary data represent a starting point for defining the gene profile of UC in different stages in Romanian population. Identification of genes implicated in UC pathogenesis could be useful to select new therapeutic targets.

Corresponding author: Teodora Ecaterina Manuc, MD, PhD Candidate; e-mail:

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21. Changes of desmin expression pattern in the myocardium of patients with alcoholic dilated cardiomyopathy

Ruxandra Camelia Deliu, Alexandru Radu Mihailovici, Ionica Pirici, Cristiana Eugenia Simionescu, Ionut Donoiu, Octavian Istratoaie, Tudorel Ciurea

Introduction: It has been suggested that desmin cytoskeleton remodeling may contribute to the progression of dilated cardiomyopathy and might affect long-term prognosis. This study is aiming at evaluating desmin expression in cardiomyocytes from patients with dilated cardiomyopathy of alcoholic etiology in advanced stages of the disease and comparing the results with measurements of normal heart tissue from control patients. Materials and Methods: For immunohistochemistry, sections from 36 myocardium fragments taken from left ventricle of dilated cardiomyopathy patients were immunolabeled with an anti-desmin antibody and negative control slides were obtained by omitting the primary antibody. We calculated the ratios between the areas of myocardiocytes and the length and number of A dark disks and assessed the desmin expression level as the integrated optical density (IOD) and, respectively, the total areas of the signal given by immunolabeling. A Student s t-test has been utilized to assess the differences, p<0.05 deemed significant data. Results: We identified significant decrease in numerical density of dark disks in our cases group compared with controls (p<0.05). Also, the ratios between total cellular area and total length of dark disks and number of dark disks was significantly different between cases and controls (p=0.04). IOD was significantly different between dilative cardiomyopathy cases and controls and also, overall desmin expression area was increased in dilatative cardiomyopathy patients. Conclusions: The identification of different desmin expression and standardization in diseased myocardium may be helpful in stratifying patients and in understanding their evolution, but also in finding new therapeutic targets that aim the alterations in desmin expression.

Corresponding author: Ionica Pirici, Teaching Assistant, MD, PhD; e-mail:

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22. Expression of E-cadherin in lung carcinoma, other than those with small cells (NSCLC)

Mirela Loredana Grigoras, Teodora Smaranda Arghirescu, Roxana Folescu, Ioana Cristina Talpos, Ciprian Mihai Gindac, Carmen Lacramioara Zamfir, Marioara Cornianu, Mirella Dorina Anghel, Codrina Mihaela Levai

It was suggested that the decrease and/or loss of E-cadherin expression in non-small cell lung cancer (NSCLC) is responsible for the development of the malignant phenotype. Moreover, clinical studies showed that the reduced expression of E-cadherin is associated with tumoral differentiation, with the presence of lymph node metastasis and with unfavorable diagnosis of patients with NSCLC. In order to evaluate if E-cadherin expression is involved in the NSCLC pathogenesis and significantly associated with clinicopathological parameters, we investigated the immunohistochemical (IHC) expression of E-cadherin in 47 lung carcinomas with tumoral resection pieces in the control peritumoral lung tissue, looking for possible correlations between the expression of this molecule and the clinicomorphological features and the evolutive prognosis of the patients. E-cadherin expression was preserved in 10 (21.28%) of the 47 NSCLCs immunostained with anti-E-cadherin antibody and reduced/absent in 37 of the 47 (78.72%) NSCLCs studied. E-cadherin plays a major role in the intercellular adhesion. The reduced expression of E-cadherin indicates an unfavorable prognosis and can be a useful prognosis factor in NSCLC - for patients with reduced expression of the E-cadherin/alpha-catenin complex, needing chemotherapy or radiotherapy.

Corresponding author: Teodora Smaranda Arghirescu, Associate Professor, MD, PhD; e-mail:; Roxana Folescu, Senior Lecturer, MD, PhD; e-mail:

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23. The anatomical and functional characteristics of parotid fascia

Delia Hinganu, Cristinel Ionel Stan, Traian Taranu, Marius Valeriu Hinganu

Parotid superficial and profound fascias are considered to originate from a bifurcation of the profound fascia. Its relations with the facial nerve, the continuity with platysma, temporal and zygomatic fascias suggest it is related to a superficial fascial complex rather with a profound one. The aim of this study is to add clues which sustain the theory of parotid fascia origin from superficial fascia of the face. The study was conducted on 12 cephalic extremities, which were meticulously dissected in the Ion Iancu Anatomy Institute of Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania, and on a group of 10 patients admitted to the Clinic of Maxillofacial Surgery, St. Spiridon Emergency Clinical Hospital, Iasi, patients which were clinically and imagistically diagnosed [computed tomography (CT), magnetic resonance imaging (MRI)] with parotid tumors and underwent surgical interventions for total or partial parotidectomy. On each stage of dissection mesoscopic images were acquired, examined and further processed to remark the regional stratigraphic differences. Surgical interventions have allowed us segmental anatomical studies, providing in vivo visualization of the fascial and muscular structures, evaluating the possibilities of dissociating the plans and appreciating their vasculature. The collected specimens were processed by paraffin technique and stained with H special techniques for muscular and connective tissue. The results are clearly showing the belonging of parotid fascia to the superficial fascia of face.

Corresponding author: Delia Hinganu, University Lecturer, MD, PhD; e-mail:; Cristinel Ionel Stan, University Assistant Professor, MD, PhD; e-mail:

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24. Keratinocyte growth factor and its receptor expression in chronic otitis media with and without cholesteatoma

Oana Elena Harabagiu, Marcel Cosgarea, Carmen Aurelia Mogoanta, Daniel Corneliu Leucuta, Alma Aurelia Maniu

Introduction: Chronic suppurative otitis media (CSOM) with and without cholesteatoma is regarded as chronic inflammation of the middle ear and mastoid mucosa that can be associated with the presence of granulation tissue and infection, which can lead to ossicular damage and hearing loss, but it is commonly known that cholesteatoma behaves aggressively. Both lesions appear to contain a predominant population of inflammatory cells, among which proinflammatory cytokines secreting keratinocyte growth factor (KGF) and its receptor (KGFR). No clear difference was demonstrated between these entities. The purpose of this study was to investigate the potential influence of KGF and KGFR in increased epithelial-cell proliferation of chronic otitis media (COM) with cholesteatoma in contrast to COM without cholesteatoma (CSOM), particularly in the granulative form, and to compare the rate of proliferation activity of epithelial cells using the Ki-67 epithelial proliferation marker expression. Patients, Materials and Methods: We analyzed 105 ears with cholesteatoma vs. 53 ears with CSOM without cholesteatoma using our KGF and KGFR variables, and the ratio of proliferating epithelial cells using Ki-67. The percentage of the specimens expressing KGF and KGFR was compared between the two groups for statistical significance using the Pearson s chi-square test. Immunohistochemical staining was conducted and the proportion of the cells staining positive for the nuclear antigen Ki-67 was evaluated in a quantitative and visual way, using light microscopes. Results: KGF was positive in 88.57% of cholesteatoma and was positive in 41.51% CSOM without cholesteatoma specimens (cholesteatoma vs. CSOM, p=0.001). The positive rate of KGFR in the CSOM group was 33.96% compared to those in cholesteatoma, which was 60.95%. Compared to the cholesteatoma specimens, a significantly smaller number of Ki-67 labeling index was detected in CSOM specimens. Conclusions: Our results indicated that the abnormal behavior of the cholesteatoma epithelium seems to be induced by the paracrine interaction between KGF and KGFR. Furthermore, we found that cholesteatoma expressing both KGF and KGFR had high Ki-67 index, which correlated with its aggressiveness. These findings suggest that excessive KGF and KGFR synthesis may contribute to the hyperproliferative state in cholesteatoma and could explain the pathological difference between cholesteatoma and CSOM.

Corresponding author: Carmen Aurelia Mogoanta, MD, PhD; e-mail:

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25. Vascular endothelial growth factor - key mediator of angiogenesis and promising therapeutical target in ulcerative colitis

Radu Bogdan Mateescu, Alexandra Eugenia Bastian, Luciana Nichita, Madalina Marinescu, Farid Rouhani, Andrei Mihai Voiosu, Andreea Bengus, Diana Rodica Tudorascu, Cristiana Gabriela Popp

Ulcerative colitis (UC) is an inflammatory bowel disease, triggered by an inappropriate immune response of colonic mucosa. Angiogenesis is an important part of inflammatory process, enhancing inflammation in a vicious circle that aggravates mucosal damage and remodeling. The most important pathway for angiogenesis in ulcerative colitis involves vascular endothelial growth factor (VEGF) and endoglin (CD105) and can be used as target for adjuvant therapy in order to improve patients outcome. We present a retrospective cohort study evaluating mucosal expression of VEGF and CD105 and their correlation with patients evolution and risk of relapse. In our study, patients with UC have correlated increases of VEGF expression and microvessel density (evaluated with CD105 staining), sustaining the hypothesis that angiogenesis is not just a passive process driven by inflammation, but an active player of mucosal lesions in ulcerative colitis.

Corresponding author: Diana Rodica Tudorascu, MD, PhD; e-mail:

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26. In-hospital and short-term prognostic factors in acute pulmonary edema: clinical and morphological features

Cristian Militaru, Cristina Maria Marginean, Carmen-Daniela Neagoe, Ruxandra Camelia Deliu, Dragos Ovidiu Alexandru, Marina Daniela Manescu, Ilona Mihaela Liliac, Constantin Militaru, Ion Rogoveanu

Introduction: There are extensive records which have included patients with acute heart failure (AHF), but specific studies about prognosis in acute pulmonary edema (PE) are scarce and have enrolled a small number of patients. The objectives of this study were to evaluate the predictive factors of short-term evolution in patients with PE. Patients, Materials and Methods: This was a prospective, two-center survey of 70 consecutive patients admitted for acute cardiogenic PE. The follow-up was performed one month after discharge. The composite endpoint was in-hospital death, and death of any cause or readmission for heart failure (HF) at one month after discharge. Heart and lung tissue analysis was performed postmortem to identify morphological features of PE. Results: In-hospital mortality was 4.2%, another 14.2% died in the first month, and an additional 10% required rehospitalization for HF. The characteristics significantly associated with end-point occurrence were: history of kidney disease, anemia, diabetes mellitus, lack of prior angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker treatment, lower systolic blood pressure (BP) at admission, lower diastolic BP at admission, creatinine at admission and at discharge, an increase in creatinine during stay, glomerular filtration rate at admission, serum sodium at admission, decrease in serum sodium during hospitalization, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) at discharge, right ventricle fractional area change, left atrium volume index. We created a multiple logistic regression model and identified five prognostic factors: age, diabetes, creatinine, diastolic BP, serum sodium. This model correctly classified 48 (96%) patients without worsening and 13 (65%) patients with worsening, providing an overall accuracy of 87.1%. Necropsy was performed on five patients and fragments of left ventricle myocardium and lung were harvested for histopathological and immunohistochemical studies. The myocardium exhibited fibrosis areas where the myocytes were completely or partially replaced by collagen fibers. Lung tissue analysis revealed some case-to-case differences, but the common finding was alveoli size larger than normal, with the lumen completely or almost completely covered by an eosinophilic liquid. Conclusions: The factors that best predicted the short-term outcome in PE were age, diabetes, diastolic BP, creatinine, serum sodium.

Corresponding author: Constantin Militaru, Associate Professor, MD, PhD; e-mail:

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27. Molecular markers in the diagnosis of invasive pituitary adenomas - an immunohistochemistry study

Ioana-Maria Moldovan, Sergiu Susman, Radu Pirlog, Elena Mihaela Jianu, Daniel Corneliu Leucuta, Carmen Stanca Melincovici, Doinita Crisan, Ioan Stefan Florian

Pituitary adenomas are benign tumors of the brain, with a relatively high prevalence in the general population, being responsible for 14.4-16.7% from all brain tumors. These tumors, although benign, have a local invasive behavior in approximately 35% of the cases. The aim of this study was to identify the differences in expression of molecular markers between primary and relapsed pituitary adenomas (as an aggressiveness indicator), as well between secreting and non-secreting pituitary adenomas. Tumor fragments were collected from 51 patients with invasive pituitary adenomas. Of these, 10 cases were operated a second time due to tumor recurrence. The tumor fragments were retrieved from the archives of the Department of Pathology, Emergency County Hospital, Cluj-Napoca, Romania. Immunohistochemical staining was performed for nine markers on 51 invasive pituitary adenomas: Ki-67, beta-catenin, E-cadherin, Bcl-2, galectin-3, p53, p27, CD117, and CD44. We compared the expression differences between two groups: the first one including primary and relapsed invasive pituitary adenomas, and another one including prolactin (PRL)-secreting and non-secreting invasive pituitary adenomas. Ki-67, p53 and Bcl-2 expressions were found significant in the PRL-secreting group. CD44 immunostaining was significant only in relapsed invasive pituitary adenomas. For the beta-catenin, E-cadherin, galectin-3, p27 and CD117 expression levels were not registered statistically significant differences between our groups. Our study is the first one to report a statistically significant difference between the expression of CD44 in primary and relapsed invasive pituitary adenomas and it could be used as a negative impact prognostic marker.

Corresponding author: Sergiu Susman, Associate Professor, MD, PhD; e-mail:

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28. The morphometry of the laryngeal phonatory system - base of the anatomical study of the voice aptitudes

Marius Valeriu Hinganu, Romica Sebastian Cozma, Paula Ciochina, Irina-Andreea Scutariu, Cristina Asimionoaiei-Simionescu, Delia Hinganu

Speaking is one of the characteristics of the human race and the main factor that has marked our progress over time. The singing voice is the crowning of the speech act and the main component of the lyrical manifestation of personality. Doctors in various fields, but especially anatomists have been concerned about discovering how the voice and the substrate of its variability are formed, but these aspects have not yet been fully deciphered. This study is the starting point in our research on the phonation system, organized on three levels: laryngeal, oral, palatinal, pharyngeal, epiglottal and nasal. We performed the dissection of seven embalmed anatomical parts, on which, we made measurements of the anatomical elements involved in the phonation. We performed the same measurements on a batch of seven adults investigated by magnetic resonance imaging (MRI). The results were entered into the statistical calculation formulas and compared with each other and with the literature. The results of the study show that certain values resulting from the calculation formulas remain constant and others vary greatly from each individuals and gender.

Corresponding author: Romica Sebastian Cozma, Lecturer, MD, PhD; e-mail:

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29. Drug-induced gingival hyperplasia - experimental model

Ancuta Goriuc, Liliana Georgeta Foia, Bogdan Minea, Alexandru Ionut Luchian, Amelia Elena Surdu, Vasilica Toma, Marcel Costuleanu, Ioana Martu

Several causes of gingival hyperplasia are known, the most widely accepted being the drug-induced gingival augmentation, a side effect associated mainly with three classes of drugs: anticonvulsants (Phenytoin), immunosuppressants (Cyclosporine A), and various calcium channel blockers (Nifedipine, Verapamil, Diltiazem). We studied the effect of Cyclosporine A (CsA) and Nifedipine on gingival fibroblasts extracted from the rat gum. Gingival fibroblasts were isolated from 6-week-old male rats weighing 150-170 g, from gingival explants, and grown in a specific culture medium consisting of Dulbecco s Modified Eagle s Medium (DMEM) supplemented with antibiotic and 10% fetal bovine serum (FBS). The medium was also supplemented with CsA (1 micro-g/mL) and Nifedipine (3 mM). We also used a control group that received no treatment. The cells were photographed at 7, 14 and 30 days, with a Nikon Eclipse TE300 phase contrast microscope. For cell viability evidence, we used immunofluorescence (flow cytometry) with a FACS (fluorescence-activated cell sorting) Calibur device and its software. We noticed that the proliferation of these cells increased with the period of drug administration, and the subsequent morphological changes that occurred were related to the presence of drug accumulations in the cell cytoplasm. Modern molecular techniques are needed to shed some light upon the pathogenesis of drug induced gingival overgrowth and, thereby, provide novel information for preventative and effective future therapeutic strategies.

Corresponding author: Vasilica Toma, Associate Professor, MD, PhD; e-mail:; Liliana Georgeta Foia, Professor, MD, PhD; e-mail:

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30. Interrelationship between oral status and histopathological aspects of periodontitis in patients from Craiova, Romania

Veronica Mercut, Shlomo Paul Zusman, Kenneth Eaton, Monica Scrieciu, Silviu-Marian Simion, Razvan-Eugen Ghita, Cristian Adrian Ratiu, Silviu Mirel Pituru, Sanda Mihaela Popescu

The aim of the present study was to evaluate the oral status in a group of institutionalized individuals from Craiova, a city in South-Western Romania. Also, another objective of the study was to highlight the clinical, histological and immunohistochemical (IHC) aspects of periodontal disorders in the elderly. The study was performed on 48 institutionalized individuals examined in the Clinic of Dental Prosthetics, Faculty of Dentistry, University of Medicine and Pharmacy of Craiova, Romania, in 2013. The data were collected using medical records and intraoral clinical examination. The data were processed by descriptive statistical analysis. The gingival mucosa samples were harvested from subjects with teeth mobility. The gingival fragments collected were processed through the histological technique of paraffin inclusion. The serial sections were commonly stained with Hematoxylin-Eosin and processed by the IHC technique with anti-CD3, anti-CD45RO and anti-CD20 antibodies. Of the 48 study participants, 20 were males, 28 were females, aged over 56 years old. 66.6% of them had poor oral hygiene, with a mean simplified oral hygiene index (OHI-S) of 1.57, 16 had the generalized periodontitis, three experienced some form of gingival overgrowth at the remaining teeth caused by incorrect fixed prosthesis, and 25 participants presented a form of periodontitis with gingival retraction. Gingival mucosa samples were histologically diagnosed with papillomatosis with discrete parakeratosis and rich chronic inflammatory infiltrate. The IHC reactions for the studied antibodies were different for T- and B-cells, which had different disposition in lamina propria.

Corresponding author: Monica Scrieciu, Professor, DMD, PhD; e-mail:; Cristian Adrian Ratiu, Associate Professor, DMD, PhD; e-mail:

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31. The Abelson tyrosine kinase (c-Abl) localization in preimplantation mouse development

Duygu Mutluay, Hakan Oner

The Abelson family member of non-receptor tyrosine kinase, c-Abl, has an important role in regulation of cellular processes like cell polarity, invasion, proliferation, survival and cell motility. In the present study, we investigated the localization of c-Abl protein during preimplantation mouse embryo development in vitro using immunofluorescence confocal microscopy. We have shown that c-Abl protein is expressed throughout all stages of preimplantation development. We found that c-Abl is asymmetrically localized in egg cortex, which suggests possible roles in positioning of the metaphase II spindle. We also observed strong c-Abl staining in external cells, especially enriched at the apical poles in morula stage and at the E3.5 stage blastocysts, cell membrane enrichment of c-Abl in trophectoderm (TE), the tissue responsible for implantation and placentation. The results indicate that c-Abl may play roles in preimplantation embryo development, especially in TE formation and differentiation.

Corresponding author: Duygu Mutluay, Assistant Professor, DVM, PhD; e-mail:

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32. Proliferation activity in bladder tumors does not correlate with the pathological grading

Mihai Lucian Stefanescu, Florin Grosu, Lucian Eugen Stoica, Michael Schenker, Laurentiu Mogoanta, Alexandra Eugenia Bastian

Worldwide, bladder cancer is the seventh most frequent cancer in men and the 17th most frequent cancer in women, respectively. In men, this type of cancer is the second most frequent type of cancer localized in the genitourinary system, after prostate cancer. The incidence of bladder cancer is ever growing and the etiopathogenic factors of bladder cancer are numerous and still not fully understood. Smoking is the most common risk factor incriminated in the onset of urinary tract cancer, the incidence of bladder cancer being directly connected to the smoking duration and the tobacco amount intake. Regarding the histopathological types, more than 90% of bladder cancer is represented by transitional cell carcinomas. Histopathology assessment of bladder cancer is a constant challenge regarding the connection between tumor grading, depth of invasion, extension and clinical prognosis. We evaluated here a number of 32 confirmed bladder tumors and we aimed to find common patterns of expression for markers like cytokeratin 7 (CK7), CK20, vascular endothelial growth factor (VEGF), CD34, matrix metalloproteinases (MMPs) 2, 8 and 9, as well as for the Ki67 proliferation index. Our study showed that both CK7 and CK20 were present in different tumor areas and tumor gradings, MMP9 was more constantly expressed compared to the more variable expression of MMPs 2 and 8, vascular densities did not seem to increase in high-grade invasive tumors compared to low-grade tumors. Interestingly, while high Ki67 proliferating indexes were present especially in high-grade superficially tumors, compared to low-grade papillary tumors; this correlation was inversed for the advancing edges of the tumor. This common feature of invasive urothelial tumors will thus require further studies in order to elucidate the cellular signaling pathways by which these tumors increase their overall invasiveness.

Corresponding author: Florin Grosu, MD, PhD; e-mail:

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33. Morphological assessment of the mandibular canal trajectory in dentate subjects

Valentin Daniel Sirbu, Paula Perlea, Vanda Roxana Nimigean, Daniela Gabriela Badita, Augustin Serban, Victor Nimigean

Background: The mandibular canal is the most important vital structure within the mandibular body. The aim of the present study was to determine the course of mandibular canal in relation to external surfaces of the mandible (buccal, lingual) and to root apices of the lateral teeth, in order to minimize the risk of its content being injured during either conservative or radical treatment of the mandibular lateral teeth. Materials and Methods: Morphometric evaluations were performed on 11 dried dentate human mandibles and on cone-beam computed tomography (CBCT) cross-sectional images of the mandible, from 18 dentate patients. By means of both methods, the following parameters were assessed: (i) the distance between the mandibular canal and the buccal (lateral) surface of the mandible (MC-BS distance); (ii) the distance between the mandibular canal and the lingual (medial) surface of the mandible (MC-LS distance); (iii) the distance between the mandibular canal and the root apices of the second premolar, the first and second molars (MC-T distance). The results were statistically processed in Stata MP/13 software package using analysis of variance (ANOVA). Results: With respect to buccal-lingual location, the mandibular canal passed horizontally through the mandibular trabecular bone, from posterior to anterior, and from lingual to lateral (buccal), and so at premolar level it approached the lateral (buccal) cortical bone plate, main topographic pattern found in 26 (89.65%) of the cases. The mandibular canal had a descending trajectory from the second molar to the first molar, after which it ascended slightly towards the second premolar, main topographic pattern found in 24 (82.75%) of the cases. Conclusions: According to the results, the second mandibular molar is the most common tooth involved in the accidental damaging of the content of the mandibular canal, during various therapeutic procedures. Overlooking the location of the mandibular canal can lead to complications in endodontic therapy and in dentoalveolar surgical procedures in the posterior region of the mandible.

Corresponding author: Vanda Roxana Nimigean, Associate Professor, DMD, PhD; e-mail:

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34. Synaptophysin expression as prognostic factor for survival in colorectal carcinomas

Diana Rodica Tudorascu, Daniel Pirici, Elena-Anca Tartea, Edme Roxana Mustafa, Cristina Florescu, Cristin Constantin Vere, Alina Maria Balea, Ileana Puiu, Georgica-Costinel Tartea, Valeria-Carmen Albu

The aim of this study is to assess the status of synapses in normal colorectal tissue compared to neoplastic colorectal tissue, and to correlate this status with survival in patients with colorectal neoplasia. Our study included 61 patients diagnosed with colorectal adenocarcinoma, representing the study group, and 53 patients diagnosed with benign conditions, that required a resection of a colorectal segment, representing the control group. We performed the immunohistochemical staining by using anti-synaptophysin antibody, which identifies synaptic vesicles and, so, we managed to analyze the expression of synapses in colorectal adenocarcinoma. Regarding both the signal area and integrated optical density (IOD) of the synaptophysin, the univariate analysis with a log-rank (Mantel-Cox) test indicated that patients with a low level of synaptophysin had a better overall survival rate than those with a high-level synaptophysin. Also, we noticed that tumor size, tumor invasion and lymph node metastasis were significantly associated with the overall survival rate, whereas the other clinicopathological features were not. In conclusion, the status of synaptic vesicles evaluated via synaptophysin expression in patients with colorectal cancer positively correlates with the survival rate and it can play a role in the neoplastic therapy process.

Corresponding author: Ileana Puiu, Associate Professor, MD, PhD; e-mail:

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35. Evaluation of brain injuries in children deceased due to head trauma

Andreea Lavinia Zorila, Marian Valentin Zorila, Marius Cristian Marinas, Razvan Stefan Tolescu, George Lucian Zorila, Charoula Florou, Marius Cristian Neamtu, Anton Knieling, Cristina Jana Busuioc

Traumatic brain injuries (TBIs) present an ever-growing prevalence, especially in the developing countries. Although 80-95% are mild to average injuries, they determine multiple severe neurological sequelae and disabilities. Most of these injuries are caused by traffic accidents. We studied a number of 29 cases of severe TBIs, in children who deceased immediately or after a few days of survival. Most of them (over 68%) were caused by traffic accidents. The incidence of traumas increased by age, most cases being recorded in the age group 10-15 years old. The TBIs were complex ones. In 86.21% of the cases, the forensic examination highlighted the presence of cranial fractures; in 93% of the cases, there were highlighted complex meningo-cerebral injuries: leptomeningeal hemorrhage associated with brain contusion injuries and with intraventricular blood flood, as well as destructive lesions of brain dilaceration; only in 7% of the cases there were highlighted meningeal lesions, with no brain lesions. The severity of the brain injuries was quite varied, according to the force of the cause agent. The histopathological and immunohistochemical examinations showed that the severity of TBIs increased according to the survival time, by adding secondary lesions caused by brain ischemia and local inflammatory reaction.

Corresponding author: Marian Valentin Zorila, University Assistant, MD, PhD; e-mail:; Marius Cristian Neamtu, Associate Professor, MD, PhD; e-mail:

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36. Carcinogenic uterine risk of repeated abortions: hormone receptors tumoral expression

Manuela Stoicescu, Simona Gabriela Bungau, Delia Mirela Tit, Gabriela Mutiu, Anamaria Lavinia Purza, Vasile Ciprian Iovan, Ovidiu Laurean Pop

The main objective of this study is to draw the attention that repeated induced abortions in the women s physiological history are very dangerous and could lead to developing uterine cancer. The legislation regarding this practice is variable in different countries. Relevant information in the field concerning the numerous risk factors that appear with abortions must be taught in schools before girls start their sexual life and can help avoiding the complications that may follow. Also, the abortion should be an extreme measure that must be used only in extreme cases that threaten the mother s life or imply the health of the future child. The study comprised 258 women diagnosed with endometrial carcinoma, without any risks factors for this type of cancer, which were questioned regarding the abortions in previous history. The results show that the age when the uterine carcinoma appears is even lower as the number of abortions is higher and the number of this type of cancer cases is directly proportional with the number of abortions suffered. In order to avoid this fact we have to pay more attention to the legislation and education of the patients. Also, we followed the expression of both estrogen and progesterone hormone receptors, in the case of uterine cancer that occurred in women who had abortions in history compared to the expression of hormone receptors in the case of patients who did not have abortions.

Corresponding author: Vasile Ciprian Iovan, Lecturer, MD, PhD; e-mail:; Simona Gabriela Bungau, Professor, PhD, Dr.habil.; e-mail:

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37. The effect of neurobiological changes in the brain of children with schizophrenia, ultra high-risk for psychosis and epilepsy: clinical correlations with EEG and neuroimagistic abnormalities

Laura Alexandra Nussbaum, Lavinia Maria Hogea, Daniela Veronica Chiriac, Mirela Loredana Grigoras, Roxana Folescu, Ana Cristina Bredicean, Elena Cecilia Ildiko Rosca, Brandon Muncan, Liliana Maria Nussbaum, Mihaela Adriana Simu, Codrina Mihaela Levai

Relatively little research has been conducted on quantitative electroencephalography (QEEG) activity in patients with psychosis/schizophrenia, especially in populations at-risk for the illness. Further studies are needed, in order to offer a possible endophenotypic marker of the cerebral functioning, associated with psychosis/schizophrenia, in correlation with the neuroimaging, the neurocognitive, biochemical, molecular genetic tests, clinical aspects and the EEG activity from the same subjects. The aim was to investigate the role the QEEG abnormalities play in the etiology of psychosis/schizophrenia, whether it can provide an endophenotype for psychosis and to make some correlations with the results obtained through magnetic resonance (MR) spectroscopy, for proper early detection and intervention. The prospective research was performed in the University Clinic of Child and Adolescent Psychiatry, Timisoara, Romania, involving 55 children with schizophrenia or ultra high-risk (UHR) for psychosis (groups 1, 2, 3 and 4) and 55 children as healthy controls (group 5). Groups 1 and 2 (28 children) are diagnosed with schizophrenia, groups 3 and 4 are UHR for psychosis (27 children), and group 5 represents healthy controls. Groups 1 and 3 had convulsive seizures in their personal history. We noticed: through the QEEG, numerous patterns of theta and delta activity, the diminished amplitude of the alpha band waves and the diminished alpha activity; also, the onset of psychosis was earlier at those presenting convulsive seizures in their personal history (groups 1 and 3); also, specific neuroimagistic abnormalities and modifications. The cerebral lesions, appearing during the development, raise the liability for schizophrenia. The high-risk for schizophrenia is correlated with the personal history of epilepsy, as well as with the family risk for psychosis.

Corresponding author: Daniela Veronica Chiriac, Senior Lecturer, MD, PhD; e-mail:; Mihaela Adriana Simu, Professor, MD, PhD; e-mail:

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38. Ectopic intracavernous corticotroph microadenoma: case report of an extremely rare pathology

Adrian Florian Balasa, Rares Chinezu, Daniel Mihai Teleanu, Maria Ionela Pascanu, Laura Chinezu, Angela Borda

Ectopic pituitary adenomas (EPAs) are most likely tumors developing from the cellular remnants following the migration of Rathke s pouch. We present the case of a 54-year-old female diagnosed with Cushing s syndrome. Magnetic resonance imaging (MRI) identified an ectopic microadenoma located in the median wall of the cavernous sinus. Microscopic transsphenoidal surgery was performed and the lesion was completely removed without any postoperative surgical complications. Based on characteristic microscopic and immunohistochemical features and on recent clinicopathological prognostic classifications, the histopathological diagnosis was non-proliferative, non-invasive corticotroph pituitary neuroendocrine tumor, grade 1a. Complete remission of disease was achieved postoperatively and was maintained for one year following surgery. MRI showed complete resection, without tumor recurrence at one and two years. Occurrence of an ectopic intracavenous adrenocorticotropic hormone (ACTH)-secreting adenoma is extremely rare and poses difficulties both in the identification, surgery, histopathological grading, and adequate endocrinological treatment and follow-up.

Corresponding author: Rares Chinezu, MD, Consultant Neurosurgeon; e-mail:

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39. Body stalk anomaly in a monochorionic-diamniotic twin pregnancy - case report and review of the literature

Roxana Elena Bohiltea, Cicerone Florentin Tufan, Monica Mihaela Cirstoiu, Adrian Vasile Dumitru, Tiberiu Augustin Georgescu, Maria Sajin, Oana Maria Bodean, Octavian Munteanu, Elvira Bratila, Anca-Maria Ofiteru, Costin Berceanu

Body stalk anomaly (BSA) is a rare abdominal defect, generally considered to be lethal. Reported prevalence ranges from 0.4 to 3.2 per 100 000 live births. An early prenatal diagnosis offers the possibility of parental counseling and the termination of pregnancy. Also called limb-body wall complex, the anomaly is characterized by finding the intrathoracic and abdominal organs outside the cavity comprised by amnio-peritoneal membrane attached directly to the placenta and the umbilical cord short or absent. We report a case of BSA in a monochorionic-diamniotic twin pregnancy, diagnosed antenatal by the massive midline thoraco-abdominal wall defect, severe scoliosis and absent umbilical cord, presented at fetal ultrasound first trimester examination; portions of the heart, kidney and lung were contained into the placenta. The second fetus was echographically normal. At 18 weeks of gestation, a recommended amniocentesis exam was performed, an abnormal karyotype being excluded through this method. At 33 weeks of gestation, the patient presented with spontaneous preterm rupture of membranes. Delivery occurred by emergency Caesarean section for acute fetal distress; extracted first live fetus was admitted in the neonatal intensive care; the second live fetus with a severe thoraco-abdominal wall defect, fragments of organs included into the placental mass and severe reduction defect of the inferior right limb, deceased at 30 minutes from delivery. The fetus together with the placenta has been sent for histopathological exam. Clinical examination confirmed the diagnosis suspected by ultrasound examination. There are only a few reports in the literature about BSA in multiple gestations, and fewer about twin pregnancies in which only one fetus was affected by this condition.

Corresponding author: Octavian Munteanu, MD, PhD; e-mail:

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40. Caruncular late-onset junctional nevus: apropos of an anatomo-clinical observation

Ovidiu Boruga, Andrei-Theodor Balasoiu, Stela Giuri, Mihnea Munteanu, Horia Tudor Stanca, Gheorghe Iovanescu, Maria-Alexandra Preda

Conjunctival nevi are benign tumors, most often located at the nasal or temporal limbus, and rarely in the fornix or tarsus. The vast majority of caruncular tumors are benign and only few are malignant. Most of the caruncular tumors (either benign or malignant) are nevi. We report a case of a 75-year-old female patient presenting caruncular atypical late-onset junctional nevus that clinically arose malignancy suspicion. Ophthalmologic macroscopic examination and slit lamp examination of the right eye were performed. Further blood tests were performed. Carunclectomy was performed two days after admission to hospital. Microscopy revealed the junctional localization, diffuse proliferation of the nevocytes. Immunoreactions with S100 and human melanoma black 45 (HMB45) antibodies were performed. Differential diagnosis of these lesions represents a great challenge. The greatest challenge represents the differential diagnosis between a benign tumor and a malignant life-threatening one, the malignant melanoma, especially with unusual presentation. The presence of a late-onset caruncular tumor with uncertain evolution requires excision biopsy to determine the diagnosis and to establish the best management.

Corresponding author: Gheorghe Iovanescu, MD, PhD; e-mail:; Andrei-Theodor Balasoiu, MD, PhD; e-mail:

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41. Uteroplacental apoplexy associated with invasive cervical neoplasm

Anca Daniela Braila, Boris Marinov Krastev, Emilia Mihai-Zamfir, Dragos Cristian Caraveteanu, Nawaf Al Krayem, Mihai Braila, Rodica Velea, Adrian Neacsu

The cervical cancer is the worldwide second neoplasia in women, after the breast cancer. The incidence of invasive carcinoma in pregnancy is 1/2000 to 1/10 000 pregnancies. In most of the studies, almost all the patients had microinvasive carcinoma or limited cervical carcinoma at the cervix level. In the uteroplacental apoplexy, pathologically, retroplacental hematoma is formed while the fetus is still in the uterus. When speaking about the uteroplacental apoplexy, the fetal mortality is 100% and the maternal mortality can reach 5%. The particularity of the presented case is the association of the invasive cervical neoplasm, pathology unknown to the patient, with uteroplacental apoplexy, diagnosis for which she was hospitalized as an emergency. After the extraction of the dead fetus by segmental-transversal cesarean section, we continued to perform the total hysterectomy with adnexectomy. The fetus, the placenta, the uterus and the ovaries were sent for histopathological examination. Subsequently, the histopathological bulletin revealed cervical lesions in the neck of type cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, metaplastic squamous epithelium and moderately differentiated squamous cell carcinoma.

Corresponding author: Anca Daniela Braila, Lecturer, MD, PhD; e-mail:

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42. Malignant melanoma of the left nasal fossa - case report

Vlad Andrei Budu, Mihail Tusaliu, Tatiana Decuseara, Cristina Maria Goanta, Cristiana Gabriela Popp, Andreea-Nicoleta Costache, Daniela Alina Popa-Cherecheanu, Carmen Aurelia Mogoanta

Mucosal malignant melanoma is an extremely rare tumor of the nose, with an aggressive character, low prognosis and frequent recurrences. The authors present a case of a 60-year-old male patient, diagnosed five years ago with adenoid cystic carcinoma, for which he had surgery and radiotherapy, who was admitted in our Clinic with unilateral epistaxis and obstruction of the nasal cavity. Clinical exam revealed an obstructive polypoidal bleeding mass of the left nasal cavity. Biopsy was performed and the histopathological exam showed malignant mucosal melanoma. Wide local endoscopic surgery was practiced for two times in the last two years, and for now, there is no recurrence. Malignant melanomas are tumors with high mortality rate, which necessitate an early diagnosis and immediate treatment.

Corresponding author: Mihail Tusaliu, MD, PhD; e-mail:

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43. Cervical adenocarcinoma generator of procoagulant status and ischemic stroke

Ana-Maria Bumbea, Magdalena-Rodica Traistaru, Stefan-Cristian Dinescu, Bogdan Stefan Bumbea, Dana-Maria Albulescu, Mihaela Niculescu, Boris Marinov Krastev, Anca-Emanuela Musetescu

The procoagulant status of neoplastic patients is well known in medical literature, but in the last years there is attempted a correlation between the histological types of neoplasia and the risk for thrombotic strokes. We present the case of a 44-years-old patient undergoing early menopause, who was diagnosed with cervical tumor of the serous adenocarcinoma type. The patient underwent external radiotherapy, and, in the seventh day of treatment, she suffered a frontal-temporal-parietal ischemic stroke with left hemiplegia. The blood testing highlighted procoagulant products (double fibrinogen compared to normal values, deficit of antithrombin and a high number of thrombocytes). The patient received neurological and rehabilitation treatment, at first with Heparin, followed by the administration of an antiaggregant. During this treatment, the deficit remained unchanged. She continued the neurological and rehabilitation treatment, followed by radiotherapy, with a good evolution. Six months after the stroke, it was decided the surgical tumor ablation of cytoreduction. The post-surgery histological examination highlighted specific changes due to post-surgery radiotherapy, without the presence of any neoplastic cells. The imagistic evaluation, computed tomography (CT) every three months after surgery, did not highlight any suggestive dissemination elements. The occurrence of an ischemic stroke in a patient with endocervical neoplasm of the adenocarcinoma type during radiotherapy imposed the discharge of chemotherapy, with subsequent imaging, biological and histopathological monitoring after surgery. The cause of stroke in this case is determined by the hypercoagulant status in the context of the developed neoplasia, the patient being free of any other risk factors.

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

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44. A rare case of mandibulary parapremolars in siblings: case report and literature review

Oana Cella Andrei, Ruxandra Margarit, Livia-Alice Tanasescu, Luminita Daguci, Catalina Farcasiu, Marilena Bataiosu, Constantin Daguci

Supernumerary teeth in permanent dentition are influenced by hereditary and environmental, having clinical variations such as location, number and morphology. Parapremolars can be found as a single supernumerary tooth or as multiple, usually in the lower jaw, sometimes in association with other types of supernumerary teeth. Familial inheritance often involves more than one generation. This paper presents a case of two brothers, one with only one parapremolar and a good oral status and hygiene, the other with poor hygiene, multiple parapremolars and one mesiodens, causing various complications. The aim of this paper is to show the presence of parapremolars in brothers with no other medical relevant history, located in the same site, and to point the influence of genetic factors in the etiology of supernumerary teeth. Along with a review of the literature, this article shows the importance of an early diagnosis and follow-up using successive panoramic radiographs of such cases, in order to limit or prevent the inflammatory, carious, periodontal and occlusal complications that can seriously affect both the jaws and the normal dentition.

Corresponding author: Marilena Bataiosu, Associate Professor, DMD, PhD; e-mail:

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45. Is thyrogastric disease a potential setting for oncogenesis? Gastric adenoneuroendocrine carcinoma arising from Helicobacter pylori-associated atrophic gastritis in a patient with autoimmune thyroiditis

Kavita Gaur, Ravindra Kumar Saran, Vineeta Vijay Batra, Puja Sakhuja, Pramod Kumar Mishra

Gastric mixed adenoneuroendocrine carcinoma arising from Helicobacter pylori-associated multifocal atrophic gastritis is exceedingly rare. An added association with autoimmune thyroiditis in this case highlighted a complex interplay between Helicobacter, autoimmunity and gastric atrophy. A 55-year-old hypothyroid female presented with hematemesis and a large polypoidal mass in the gastric fundus, suggestive of gastrointestinal stromal tumor on imaging and endoscopy. Histopathology revealed a tumor comprised of nests of monomorphic cells immunopositive for synaptophysin and chromogranin A admixed with malignant glands. Follow-up imaging revealed a heterogeneously enhancing residual gastric body wall. A completion total gastrectomy was performed. Histopathology displayed multifocal atrophic gastritis, occasional Helicobacter and nests of neuroendocrine cells. The patient also had markedly elevated levels of anti-thyroid peroxidase and anti-thyroglobulin. To the best of our knowledge, this is the first case of gastric adenoneuroendocrine carcinoma arising from H. pylori-associated atrophic gastritis, in a patient with autoimmune thyroiditis.

Corresponding author: Ravindra Kumar Saran, MD, D.N.B, Director Professor; e-mail:

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46. Rare metastasis of renal carcinoma in the frontoethmoid-orbital region - case report and review of the literature

Razvan Hainarosie, Florin Anghelina, Irina Gabriela Ionita, Olimpia Iulia Zoican, Catalina Pietrosanu, Silviu Mirel Pituru, Viorel Zainea

A tumor located in the region of the paranasal sinuses and the orbit is not usually a metastasis, but a primary tumor. Even more, renal cell carcinoma (RCC) is very rarely the cause of metastasis in the paranasal sinuses or the orbit. Up to the present moment, few cases have been reported in the literature of such an association. The aim of the authors is to highlight the rare case of a male patient presented with ptosis, frontal swelling, minor headaches and epistaxis, as the only symptoms, but in which the mass located in the left frontoethmoidal region with extension to the orbit proved to be a RCC metastasis, thus leading to the diagnosis of the primary renal tumor. We must underline the need for clinical suspicion and the importance of accurate histopathological and immunohistochemical investigations, in such rare cases, where they are crucial in obtaining the right diagnosis.

Corresponding author: Florin Anghelina, Associate Professor, MD, PhD; e-mail:

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47. Rare case of single coronary artery in a patient with liver cirrhosis

Eugen Nicolae Tieranu, Ionut Donoiu, Octavian Istratoaie, Alice Elena Gaman, Maria Loredana Tieranu, Cristian George Tieranu, Dan Ionut Gheonea, Tudorel Ciurea

We report here the case of a 58-year-old male presented with atypical chest pain, dyspnea and fatigue, with a medical history of liver cirrhosis and undergoing treatment with beta-blocker. The clinical exam was normal. The 12-lead electrocardiogram (ECG) showed normal heart rate, without repolarization changes. Transthoracic echocardiography revealed no wall motion abnormalities of the left ventricle, moderate tricuspid regurgitation with mild pulmonary hypertension and left ventricular hypertrophy. The biochemical markers for myocardial infarction were negative. He underwent coronary angiography that revealed a single coronary artery originating from the right coronary sinus of Valsalva.

Corresponding author: Ionut Donoiu, Assistant Professor, MD, PhD; e-mail:

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48. A rare case of clear-cell carcinoid of appendix

Andreea Iliesiu, Narcis Octavian Zarnescu, Alexandru Chirca, Eugenia Claudia Zarnescu, Irena Antonia Ungureanu, Stefan Ilie Neagu, Radu Virgil Costea

The carcinoids are the most frequent type of tumors arising from the appendix. In the majority of cases, these tumors are asymptomatic and usually are discovered after appendectomy. Definitive diagnosis relies on pathological examination of the resected appendix, size of the tumor being critical for the further management. Clear-cell change in neuroendocrine tumors (NETs) has rarely been described in the appendix. We choose to present a clear-cell carcinoid subtype of appendiceal NET to raise awareness on this potentially curable and rare condition that can be overlooked. We highlight the importance of the pathological exam and the morphological and immunohistochemical behavior of the tumor in confirming the diagnosis and aiding in the treatment decision making. Also, important entities should be considered in the process of differential diagnosis such as goblet-cell carcinoid or renal-cell/ovarian carcinoma.

Corresponding author: Narcis Octavian Zarnescu, Lecturer, MD, PhD; e-mail:

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49. Diagnosis and management of a young woman with acute isolated lateral sinus thrombosis

Dragos Catalin Jianu, Silviana Nina Jianu, Andrei Gheorghe Marius Motoc, Marioara Poenaru, Ligia Petrica, Adrian Vlad, Sorin Ursoniu, Anca Elena Gogu, Traian Flavius Dan

Isolated lateral sinus thrombosis (LST) was mentioned in the past as a complication of middle ear infection. In the recent years, it was not frequently studied. Our patient, a 23-year-old woman who was taking an oral contraceptive pill, displayed 24 hours of migraine, such as headache; her systemic examinations were normal. She underwent neuroimaging examinations in the first 36 hours of admission. Native head computed tomography (CT) revealed hyperdensities along the left tentorium, involving the left lateral sinus (LS). Cranial magnetic resonance imaging (MRI) showed hypointense signal on MRI T2 SW (susceptibility-weighted) in the region of the left LS. MR venography noted the absence of flow-related signal within the left LS. The clinical symptoms, signs and neuroimaging results formulated the diagnosis of left isolated LS thrombosis. Laboratory data demonstrated an elevated D-dimer and homozygosity for the factor V Leiden mutation. She was immediately started on anticoagulation in the form of low-molecular-weight Heparin; then, she was treated with Warfarin for an indefinite duration. The headaches resolved within two days and her neurological examination was also normal. A second MR venography achieved after two weeks demonstrated complete recanalization of the venous sinuses. We did not observe any LST recurrence, deep vein thrombosis or pulmonary embolism during one year of follow-up. The early initialization of anticoagulation produced a favorable evolution. An acute isolated left LST could be identified in her case on the head CT combined with MRI and MR venography.

Corresponding author: Andrei Gheorghe Marius Motoc, MD, PhD, Specialist in Obstetrics-Gynecology, Professor of Anatomy; e-mail:

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50. Invasive keratinizing squamous cell carcinoma of the left external auricular canal and the middle ear - case report

Danut Dinca, Gabriela Izabela Baltatescu, Cherana Gioga, Elena Sapte

The rather low incidence of auricular neoplasms irrespective of localization is likely to cause confusion of diagnosis with the more frequent benign ear pathology. Because of this, the elapsed time until confirmation of the diagnosis facilitates the evolution of the disease to the detriment of the patient s health. The diagnosis of an ear neoplasm can hide under the ordinary appearance of external otitis, chronic otorrhea or episodes of various types of ear pain. Evolution of such a malignant pathology is quite rapid and highly aggressive locoregional complications are the subject of discussions regarding the interpretation of the results of paraclinical tests and the medical-surgical treatment approach that must take into account the histological structure, the size of the tumor, and the invasion of neighboring tissue.

Corresponding author: Cherana Gioga, DMD, PhD; e-mail:; Elena Sapte, Associate Professor, MD, PhD; e-mail:

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51. A histopathological diagnosis of mesenteric cystic lymphangioma, clinically misdiagnosed as simple mesenteric cyst - case report

Elena Hanganu, Simona-Lacramioara Gavrilescu, Mioara-Florentina Trandafirescu, Ana-Maria Chiforeanu, Doina Mihaila, Irina-Daniela Florea, Dana-Teodora Anton-Paduraru, Marin Burlea

Abdominal cystic lymphangiomas are relatively rare congenital malformations, predominantly found in the pediatric age group. They are usually found in the head and neck of affected children. Lymphangioma of the small-bowel mesentery is rare, having been reported for less than 1% of all lymphangiomas. The gross and histopathological findings may resemble benign multicystic mesothelioma and lymphangiomyoma. The immunohistochemical study for factor VIII-related antigen, D2-40, calretinin and human melanoma black-45 (HMB-45) is essential for diagnosis. Factor VIII-related antigen and D2-40 are positive in lymphangioma but negative in benign multicystic mesothelioma. HMB-45 shows positivity in the smooth-muscle cells around the lymphatic spaces of the lymphangiomyoma. This report describes a case of a large mesenteric lymphatic cyst identified in the neonatal period. Early diagnosis was possible due to the prenatal imagistic methods. Fetal ultrasound identified in the 17th week of gestational life an abdominal tumor that increased with fetal growth. The anatomopathological differential diagnosis and modalities of treatment are also discussed.

Corresponding author: Dana-Teodora Anton-Paduraru, Lecturer, MD, PhD; e-mail:

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52. Morphological and genetic abnormalities in a Jacobsen syndrome

Alexandru Daniel Jurca, Kinga Kozma, Mihai Ioana, Ioana Streata, Codruta Diana Petchesi, Marius Bembea, Maria Claudia Jurca, Emilia Albinita Cuc, Cosmin Mihai Vesa, Camelia Liana Buhas

Jacobsen syndrome (JS) is a contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. The syndrome is rare and there are very few observations regarding the pubertal period of the affected individuals. We report the case of a 22-year-old female, with JS, monitored since the age of three months. She presented intrauterine growth retardation, failure to thrive and feeding difficulties from the first year of the life, and she learned to walk at the age of four years. Phenotypically, the case is characterized by distinctive facial and limb abnormalities. She shows spasticity and profound delay in gross and fine motor skills. Additionally, she has severe learning difficulties, non-verbally communicates, and displays hetero-aggressive and auto-aggressive behavior. The evolution of puberty was characterized by hypogenitalism and primary amenorrhea. Thrombocytopenia and IgM deficiency became apparent also at puberty. Array comparative genomic hybridization (aCGH) analysis confirmed a deletion of 16.3 Mb on 11q23.3-q23.4. We report this case as the first documented case of JS in Romania, as well as for clinical particularities (long period of survival and late appearance of hematological and immunological disorders).

Corresponding author: Maria Claudia Jurca, Lecturer, MD, PhD; e-mail:

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53. Acute lithiasic cholecystitis, pseudoneoplastic form, a cause of conversion for laparoscopic cholecystectomy

Ana-Maria Predoi, Dan Gabriel Mogos, Dan Lucian Stefan Mogos, Stelian Stefanita Mogoanta, Mihaela Tenovici, Marius Cristian Neamtu, Nina Ionovici, Gabriel Florin Razvan Mogos

Acute lithiasic cholecystitis represents one of the most frequent pathologies of the digestive tract, most often requiring emergency surgical treatment. The prevalence of this condition increases with age and it affects women the most. Laparoscopic cholecystectomy is the preferred surgical treatment, as it diminishes postoperatory pain, it reduces the hospitalization period and medical and social costs, and it also provides a rapid postoperatory recovery. We present the case of an elder female patient, who presented with complex symptoms and signs, suggesting both lithiasic cholecystitis and a gallbladder neoplastic condition. Although there was preferred a laparoscopic cholecystectomy, the presence of an inflammatory process with intense sclerous reaction in the hepatocystic triangle led the conversion of laparoscopic cholecystectomy into an open, classical one. Due to the inflammatory process, the common bile duct (CBD) could not be explored. The subsequent practicing of a cholangiography on the drain tube highlighted the presence of an obstacle in the end zone of the CBD, which could not be removed until the second surgical intervention. The histopahological exams - from frozen sections to immunohistochemistry - had a crucial role in deciding patient s surgical management. The good evolution of the case and the final postoperatory result confirmed that the therapeutic manner chosen for this case was the appropriate one.

Corresponding author: Stelian Stefanita Mogoanta, Associate Professor, MD, PhD; e-mail:; Marius Cristian Neamtu, Associate Professor, MD, PhD; e-mail:

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54. Rare sinonasal lesions

Cristian Andrei Sarau, Marioara Poenaru, Nicolae Constantin Balica, Flavia Baderca

Rare naso-sinonasal lesions represent a diagnostic challenge for clinicians because of the paucity of the cases and similarities with other more frequently sinonasal pathologies. The aim of the study was to present five rare sinonasal lesions in order to emphasize their symptomatology, imaging aspects, histopathological features, algorithms of diagnosis, and strategies of treatment and importance of teamwork between clinicians, pathologists and radiologists for a correct and prompt diagnosis. Case presentations: The cases were represented by patients with nasal sarcoidosis, nasal primitive neuroectodermal tumors, sinonasal mucosal melanoma, sinonasal plasmacytomas and nasal-type extranodal natural killer (NK) T-cell lymphoma. All the patients were biopsied in the Department of ENT (Ear, Nose and Throat), Victor Babes University of Medicine and Pharmacy, Timisoara, Romania, and the diagnosis was made using routine and immunohistochemical (IHC) stainings. The patients with sinonasal melanoma and the patient with extranodal NK T-cell lymphoma died in few months after diagnosis, despite treatment. Rare sinonasal lesions share similar symptomatology and imaging aspects with other, more frequently diagnosed entities. The cases reported in this paper showed the same pattern as those presented in other studies; the symptomatology, diagnosis, treatment and prognosis were the same. Clinical examination, imaging studies and routine and IHC markers guides us to the right diagnosis that should be prompt because of the prognosis of some tumors. The treatment has a few characteristics: surgery excision within safe margins, working with other specialties (oncology, radiotherapy, hematology, nephrology, pneumology), follow-up and correctly informing the patient being mandatory. Conclusions: In this paper, there were presented five interesting cases of rare sinonasal lesions, in order to highlight the importance of teamwork for a quick and correct diagnosis.

Corresponding author: Nicolae Constantin Balica, Assistant Professor, MD, PhD; e-mail:

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55. Subdural hematoma - a cause of death in the development of a prostatic adenocarcinoma with dural metastases: case report

Anton Knieling, Madalina Maria Diac, Laura Adriana Riscanu, Roxana Eugenia Zavoi, Diana Bulgaru Iliescu

Non-traumatic subdural hematoma secondary to dural metastases is a rare complication. Dural metastases from a prostate adenocarcinoma occur in the advanced stages of this pathology and may sometimes be the first manifestation of a prostate carcinoma. Less than 40 cases of subdural hematoma are reported in the literature as a consequence of dural metastases from a prostate adenocarcinoma. The authors present the case of a male patient diagnosed with stage IV prostate adenocarcinoma with bone metastasis, who is admitted for left hemisphere subdural hematoma with right hemiparesis. The evolution of the patient is unfavorable, and the autopsy shows dural metastases and a collection of subdural coagulated blood. The chronic subdural hematoma with re-bleeding is a rare cause of death in the development of a prostate adenocarcinoma.

Corresponding author: Roxana Eugenia Zavoi, Professor, MD, PhD; e-mail:; Madalina Maria Diac, Teaching Assistant, MD, PhD Student; e-mail:

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56. Cyclopia and proboscis - the extreme end of holoprosencephaly

Andrei Mihai Malutan, Marina Dudea, Razvan Ciortea, Mihaela Muresan, Carmen Elena Bucuri, Carina Mihu, Dan Mihu

Holoprosencephaly (HPE), a major congenital abnormality in brain development is characterized by the absence or incomplete cleavage of prosencephalon into separate hemispheres, with cyclopia as the extreme manifestation of HPE, presenting as a failure of embryonic prosencephalon to properly divide the orbits of the eye in two cavities. We report the case of a 15-year-old pregnant patient, who delivered a 34-week living fetus with alobar HPE, cyclopia and proboscis. The patient did not have any routine scans during pregnancy; her first obstetrical exam was performed at 29 weeks of gestation (WG), when a prenatal ultrasound found a fetus with alobar HPE, cyclopia, proboscis, polydactyly and single umbilical artery. Despite adequate medical and genetic counseling, the patient and her legal representative refused further investigations - magnetic resonance imaging and genetic testing. She was admitted to the hospital at 34 WG for premature rupture of membranes, with clear amniotic fluid. Twenty-four hours later, she delivered vaginally a living male fetus, weighing 1995 g. Macroscopic examination revealed umbilical cord with two vessels, fetal proboscis, cyclopia, low implanted ears, bilateral polydactyly of the upper limbs, spina bifida occulta in the sacral region. The newborn lived for 40 minutes. Microscopy of the eyeball revealed choroid, ciliary body and conjunctiva structures, with no identification of the retina, and no evidence of the optic nerve in the fragments obtained from the optic chiasm region. This case underlines the importance of early obstetrical examinations during pregnancy and raises concerns about the ethics of allowing therapeutic termination of pregnancy after 24 WG in selected cases.

Corresponding author: Marina Dudea, MD, PhD Student; e-mail:

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57. Occurrence of invasive cervical resorption after the completion of orthodontic treatment

Paula Perlea, Marina Imre, Cristina-Coralia Nistor, Mihaela-Georgiana Iliescu, Irina-Maria Gheorghiu, Itzhak Abramovitz, Alexandru-Andrei Iliescu

The invasive cervical resorption (ICR) is an irreversible and progressive loss of tooth hard tissues involving coronal and root dentine that usually affects single permanent teeth. The aim of this study was to present the pattern of ICR lesions detected in three patients with no contributory medical and dental anamnesis, at different time periods after orthodontic tooth movements. Conventional radiographs and cone-beam computed tomography (CBCT) images were obtained by X-Mind (Satelec), respective 3D Accuitomo (Morita). The present clinical study confirmed that orthodontic forces might be a key factor for generating an ICR and the risk of lesion occurrence is increased in long movements of the teeth because the orthodontic forces act continuously an extended time. However, it should not be overlooked the synergistic effect of additional factors such as traumatic injuries, periodontal inflammation, clenching, and grinding. The more advanced ICR lesions found in our study, described as Heithersay Class 3 and Class 4, appeared on conventional radiographs as irregular, diffuse, mottled radiolucencies extended both to the crown and deeply into the tooth root. CBCT proved to have a superior accuracy in detection and assessing the severity of ICR, since the conventional intraoral radiographs cannot afford an early and proper identification of the resorptive defect. Moreover, the CBCT image allows an accurate inspection of all surfaces of tooth due to the slices in sagittal, axial and coronal planes, and to avoid erroneous diagnostic conclusions. Currently, due to CBCT scan, the nature and extension of ICR lesion into the tooth structures can be exactly evaluated.

Corresponding author: Irina-Maria Gheorghiu, DDS, PhD; e-mail:

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58. Long-term survival in a patient with advanced gastric cancer and metachronous right-sided colon cancer

Anca Sava, Delia Gabriela Ciobanu Apostol, Elena Sapte, Lidia Ionescu, Claudia Florida Costea, Manuela Ciocoiu, Gabriela Florenta Dumitrescu, Cristinel Ionel Stan, Ana Maria Slanina, Roxana Gabriela Cobzaru, Irina Iuliana Costache

Gastrointestinal carcinomas represent the most common cancers worldwide. The coexistence of gastric cancer with metachronous colon cancer represents a rare phenomenon, and the prognosis of the patient is poor. We present here a case of an elderly patient with primary gastric intestinal type well-differentiated adenocarcinoma (pT3N0, stage IIA) who developed a metachronous right-sided colon cancer diagnosed and treated after 11 years from the first surgical intervention. Histopathological and immunohistochemical examination revealed a well-differentiated adenocarcinoma (strongly positive staining for cytokeratin 20 and CDX2), pT3N0 stage IIA. The patient is still alive and active after 16 years from his first surgical intervention, even though no treatment has done after the removal of his second cancer. In conclusion, in any case of gastric cancer, first the surgeon, and then the general practitioner should be alert to recognize a second primary tumor with different origin and to perform complete postoperative control. The correct diagnosis could lead to the patients best prognosis.

Corresponding author: Delia Gabriela Ciobanu Apostol, MD, PhD; e-mail:; Elena Sapte, MD, PhD; e-mail:

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59. Extranodal NK/T-cell lymphoma, nasal type with cutaneous involvement - a rare case associated with chronic C hepatitis and occupational metal dust exposure

Eugen Horatiu Stefanescu, Nicolae Constantin Balica, Ioana Delia Horhat, Flavia Baderca, Marius Octavian Pricop, Horatiu Constantin Urechescu, Daniel Florin Lighezan, Cristian Andrei Sarau

Extranodal natural killer (NK)/T-cell lymphomas, nasal type are rare and aggressive non-Hodgkin s lymphomas (NHLs), with unknown etiology, rapid evolution and poor prognosis, due to midline tissue destruction and rapid spreading of the tumor. These lymphomas occur commonly in the nasal cavity and upper aerodigestive tract, but can also present involvement of the skin, salivary gland, and testis. We describe a case of nasal type T-cell NHL involving the nasal cavity and determining right thigh cutaneous metastases in a 47-year-old female associated with liver comorbidities and occupational dust exposure. The patient was suffering from chronic type C hepatitis and cirrhosis and she has been occupationally exposed to metal dust for 10 years. Clinical and laboratory investigations were performed. Essential for diagnosis and treatment protocol was nasal endoscopy and biopsy of nasal and cutaneous lesions. The histopathological exam was consistent with NK/T-cell lymphoma. Patient was diagnosed in Ann Arbor stage IVA. Chemotherapy was initiated with Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine and Prednisone, but it was stopped after two cycles because of the liver condition. The treatment plan also included radiotherapy, but soon after initiation, the patient died because of a liver complication. We present a rare case of extranodal NK/T-cell lymphoma, nasal type, with cutaneous involvement to which the treatment could not be properly applied because of the late diagnosis and liver comorbidities.

Corresponding author: Flavia Baderca, Associate Professor, MD, PhD; e-mail:

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60. Solitary Langerhans histiocytosis of the orbit: case report and review of the literature

Alina Simona Sovrea, Dana Monica Bartos, Adrian Bartos, Eleonora Dronca, Bianca Aurora Szabo

Langerhans cell histiocytosis (LCH), previously known as histiocytosis X, is a clinical entity characterized by abnormal proliferation of Langerhans cells, which exert a mass effect. Orbital involvement due to LCH is rare as a unifocal disease, seldom occurring outside the pediatric population. We report a case of a 21-year-old man with solitary LCH of the orbit depicted by magnetic resonance imaging (MRI) and diagnosed by histopathological examination.

Corresponding author: Eleonora Dronca, MD, PhD; e-mail:

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61. Mesenteric panniculitis, a rare cause of acute surgical abdomen in children. Case report and literature review

Elena Tarca, Mioara-Florentina Trandafirescu, Elena Cojocaru, Doina Mihaila, Bogdan Savu

Mesenteric panniculitis appears as a less known benign condition due to its infrequency and not fully elucidated etiology; currently, less than 20 cases in children have been reported. It is characterized by a fibrotic and inflammatory transformation of the mesentery fat of the small intestine and, less commonly, of the colon. The 8-year-old patient whose case we report presented in our Service complaining of acute digestive symptoms. A causality relation with the small yet frequent injuries the child suffered at the abdominal level during his sports practice may be hypothesized, although this correlation cannot be proven. Laboratory test values are usually within the normal range in such patients, yet the inflammatory values are sometimes high, just as in our case. The imagistic diagnostic workup detected a solid mass at the level of the hepatic colic flexure, with a non-homogenous structure, with fine contrast uptake in the walls; perilesional fatty infiltration with misty mesentery appearance; infracentimetric adenopathies located in the mesentery root. The tumor was surgically excised and intestinal anastomosis was performed. Achieving the final pathological diagnosis of mesenteric panniculitis was a difficult task, as it required several differential diagnoses, by ruling out a local vasculitis process and an idiopathic inflammatory Crohn s-like disease. The patient s post-operative evolution was positive. The follow-up examinations at one month, six months, one year and two years showed a good general condition, a good nutrition state and clinical-paraclinical test results within normal values. A significant association of mesenteric panniculitis to other malignancies, as well as a predisposition of these patients to the subsequent occurrence of neoplasms has been noted in adults. As these findings have not yet been proven in children, due to the small number of cases and the absence of prospective studies, long-term monitoring is an absolute must.

Corresponding author: Mioara-Florentina Trandafirescu, Lecturer, MD, PhD; e-mail:

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62. Keratoacanthoma of the conjunctiva - case report and review of the literature

Bianca Aurora Szabo, Alina Simona Sovrea, Dana Monica Bartos, Adrian Bartos, Carmen Georgiu

Introduction: Keratoacanthoma (KA) is a relatively common, benign, rapidly growing and self-limiting squamous proliferation, which appears most frequently on the sun-exposed skin. The nature of KA and its relationship to squamous cell carcinoma (SCC) still represent one of the major debates in dermatopathology, as it is the truthfulness of such a diagnosis outside the skin. However, the tumor is now known to originate from the pilosebaceous units of the skin or from ectopic sebaceous glands of squamous mucous membranes, and to differentiate onto follicular isthmus/infundibulum-like epithelium. Case presentation: A 71-year-old man presented with a sore and red right eye, which on slit-lamp biomicroscopical examination revealed a dome-shaped lesion at the temporal inferior conjunctival limbus. After a thorough histopathological examination, a diagnosis of KA has been made, both after the initial tumor excision and after the relatively rapid recurrence. After the second intervention, no recurrence was observed over five years of follow-up, confirming the diagnosis. Conclusions: The peculiarity of the case stands in his exceptional rarity, being to our knowledge the first conjunctival KA reported in our country. In the light of current knowledge, the peculiar limbal location of all the conjunctival KAs reported in the literature raised the question of the possible role of limbal stem cells in the histogenesis of these tumors, similar to the pilosebaceous ones. The treatment of conjunctival KA remains the complete excision of the tumor, as it allows histopathological evaluation of the entire tumor and the exclusion of a KA-like SCCs or KAs with SCC component.

Corresponding author: Alina Simona Sovrea, Associate Professor, MD, PhD; e-mail:

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63. Vulvar eccrine porocarcinoma: report of a case and literature review

Jose-Fernando Val-Bernal, Sandra Hermana

Adnexal carcinomas of the vulva are rare tumors. A case of an 83-year-old woman with a 3.5 cm vulvar lobulated mass that grew over an 18-month period is reported. Histopathological examination of the initial biopsy revealed a poorly differentiated infiltrating carcinoma. Treatment included radical vulvectomy with bilateral inguinal lymphadenectomy. The histological examination of the vulvectomy specimen resulted in eccrine porocarcinoma (EPC) diagnosis. A review of the literature disclosed eight vulvar cases previously reported. The study of the nine cases including the present revealed that the ages of the patients ranged from 32 to 88 years, with a mean of 66.1 years. The location of the tumor was most common in the labium majus. The size ranged from 2 cm to 5 cm (mean 3.3 cm). A longstanding history suggested that at least two (22.2%) tumors arose from a preexistent benign eccrine poroma. Considering the reduced prevalence of EPC, the diagnosis of this type of tumor is challenging. The follow-up varied from six to 132 months (mean 35.2 months). Two (22.2%) tumors recurred, three (33.3%) patients developed regional lymph node metastases, and two (22.5%) patients showed distant metastases. Only one patient died of the disease, two patients remained alive with tumor, and four (44.4%) patients showed no evidence of disease. Although a rare entity, EPC should be considered in the differential diagnosis of a vulvar mass. In the vulva, it is difficult to establish the clinicopathological predictors of prognosis of EPC. However, the markers of aggressiveness at extragenital sites may also apply to this vulvar tumor.

Corresponding author: Jose-Fernando Val-Bernal, MD, PhD; e-mail:

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64. Maxillary distomolars: case reports, differential diagnosis and literature review

Constantin Daguci, Mihai Burlibasa, Ruxandra Margarit, Livia-Alice Tanasescu, Luminita Daguci, Marilena Bataiosu, Monica Scrieciu, Oana Cella Andrei

Supernumerary teeth can be found anywhere in the oral cavity, during deciduous or permanent dentition, in males and females. They are rare, owned to various genetic or environmental factors and usually impacted. This article first reports three cases of young adult patients coming to the office for other reasons than their maxillary distomolars and without any pathology caused by them. The decision of keeping or removing these teeth was made based on other associated factors. The fourth case is one of a 40-year-old partially edentulous male patient, also with a good general health and no other associated condition, having a unilateral maxillary fourth molar; it was small, only partially erupted, with a normal morphology with crown and root and an impacted perpendicular position on the distal face of the third molar. It was extracted because of the periodontal and carious complications that it caused to the third molar facing it. The last reported case is a 64-year-old partially edentulous female patient with a maxillary tooth very similar to a distomolar because of its form and position; it was extracted because it interfered with the new removable partial denture treatment plan. The differential diagnosis between a distomolar and an anatomical variant of a third molar was difficult to make even using panoramic X-ray, also because of a very small inferior third molar. In young patients, distomolars are rather accidentally discovered during radiographic examination; later in life, they can cause both pathological issues and difficulties in diagnosis and prosthetic treatment.

Corresponding author: Luminita Daguci, Associate Professor, DMD, PhD; e-mail:

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65. Scientific and organizational achievements of Professor of Anatomy Henryk Kadyi - Rector Vigilantissimus Universitatis Leopoliensis

Andrzej Wincewicz, Monika Turek-Pietrzykowska

Henryk Kadyi (1851-1912) was educated in medicine at Jagiellonian and Vienna Universities, who deepened his studies in Leipzig to obtain associate professorship in descriptive anatomy at Alma Mater Cracoviensis, in 1878. He was elected Rector of Lvov University for years 1898-1899. Kadyi organized emerging Academy of Veterinary Medicine and Faculty of Medicine in Lvov. He equipped them with excellent anatomical facilities, e.g., remarkable collections of anatomical specimens. Kadyi worked out plans and such a detailed curriculum of higher studies in veterinary medicine, that it was raised to the ranks of academic discipline. He profoundly described accessory praehyoid and suprahyoid remnants of thyroid tissue and reasoned the anatomic term of arteria radicularis magna for artery of Adamkiewicz. Kadyi s social endeavors enabled women an access to higher education and university employment in 1895. His academic foresight, thrift and vigilance made Kadyi deserve a title of Rector Vigilantissimus.

Corresponding author: Andrzej Wincewicz, MD, PhD, Associate Professor of Pathology, FEBP (Fellow of European Board of Pathology); e-mails:,

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66. Conference Announcement: The 16th National Symposium of Microscopic Morphology, with international attendance, May 23rd-26th, 2018, Craiova, Romania

Laurentiu Mogoanta

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