ROMANIAN JOURNAL of MORPHOLOGY and EMBRYOLOGY

Vol. 65 No. 2, April-June 2024

1. Metallic nanomaterials - targeted drug delivery approaches for improved bioavailability, reduced side toxicity, and enhanced patient outcomes

George-Alexandru Croitoru, Diana-Cristina Pirvulescu, Adelina Gabriela Niculescu, Alexandru Mihai Grumezescu, Alexandru Mihai Antohi, Carmen-Larisa Nicolae

This paper explores the integral role of metallic nanomaterials in drug delivery, specifically focusing on their unique characteristics and applications. Exhibiting unique size, shape, and surface features, metallic nanoparticles (MNPs) (e.g., gold, iron oxide, and silver NPs) present possibilities for improving medication efficacy while minimizing side effects. Their demonstrated success in improving drug solubility, bioavailability, and targeted release makes them promising carriers for treating a variety of diseases, including inflammation and cancer, which has one of the highest rates of mortality in the world. Furthermore, it is crucial to acknowledge some limitations of MNPs in drug delivery before successfully incorporating them into standard medical procedures. Thus, challenges such as potential toxicity, issues related to long-term safety, and the need for standardized production methods will also be addressed.

Corresponding author: Adelina Gabriela Niculescu, Chem Eng, PhD Student; e-mail: adelina.niculescu@upb.ro

Abstract   Open Paper   Download PDF

2. The role of FGF21 in the interplay between obesity and non-alcoholic fatty liver disease: a narrative review

Cristina Elena Negroiu, Robertina Iulia Tudorascu, Maria Cristina Bezna, Adrian Ionut Ungureanu, Sorina Octavia Hontaru, Suzana Danoiu

Obesity poses a significant and escalating challenge in contemporary society, increasing the risk of developing various metabolic disorders such as dyslipidemia, cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD), type 2 diabetes, and certain types of cancer. The current array of therapeutic interventions for obesity remains insufficient, prompting a pressing demand for novel and more effective treatments. In response, scientific attention has turned to the fibroblast growth factor 21 (FGF21) due to its remarkable and diverse impacts on lipid, carbohydrate, and energy metabolism. This comprehensive review aims to delve into the multifaceted aspects of FGF21, encompassing its discovery, synthesis, functional roles, and potential as a biomarker and therapeutic agent, with a specific focus on its implications for NAFLD.

Corresponding author: Robertina Iulia Tudorascu, Lecturer, MD, PhD; e-mail: irtudorascu@gmail.com; Sorina Octavia Hontaru, Lecturer; e-mail: dr.octavia1969@yahoo.com

Abstract   Open Paper   Download PDF

3. Silica nanoparticles in medicine: overcoming pathologies through advanced drug delivery, diagnostics, and therapeutic strategies

Carmen-Larisa Nicolae, Diana-Cristina Pirvulescu, Alexandru Mihai Antohi, Adelina Gabriela Niculescu, Alexandru Mihai Grumezescu, George-Alexandru Croitoru

Over the last decades, silica nanoparticles (SiNPs) have been studied for their applications in biomedicine as an alternative used for conventional diagnostics and treatments. Since their properties can be modified and adjusted for the desired use, they have many different potential applications in medicine: they can be used in diagnosis because of their ability to be loaded with dyes and their increased selectivity and sensitivity, which can improve the quality of the diagnostic process. SiNPs can be functionalized by targeting ligands or molecules to detect certain cellular processes or biomarkers with better precision. Targeted delivery is another fundamental use of SiNPs. They could be used as drug delivery systems (DDS) since their structure allows the loading of therapeutic agents or other compounds, and studies have demonstrated their biocompatibility. When SiNPs are used as DDS, the drug s toxicity and the off-target effects are reduced significantly, and they can be used to treat conditions like cancer and neurological diseases and even aid in regenerative processes, such as wound healing or bone repair. However, safety concerns must be considered before SiNPs can be used extensively in clinical practice because NPs can cause toxicity in certain conditions and accumulate at undesired locations. Therefore, an overview of the potential applications that SiNPs could have in medicine, as well as their safety concerns, will be covered in this review paper.

Corresponding author: Adelina Gabriela Niculescu, Chem Eng, PhD Student; e-mail: adelina.niculescu@upb.ro

Abstract   Open Paper   Download PDF

4. Prognostic implications of immunohistochemistry in patients with endometrial cancer

Maria-Bianca Anca-Stanciu, Andrei Manu, Maria Victoria Olinca, Bogdan Catalin Coroleuca, Diana-Elena Comandasu, Ciprian Andrei Coroleuca, Calina Maier, Elvira Bratila

Various histological cell types, high histological grade, extensive myometrial invasion, and the presence of lymphovascular involvement are recognized as risk factors for disease development. Individuals carrying mutations in MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), or postmeiotic segregation increased 2 (PMS2) genes face an increased susceptibility to both endometrial and colorectal malignancies, with a lifetime risk ranging from 40% to 60%. This research aimed to investigate the prevalence of specific immunohistochemical (IHC) markers and microsatellite instability in endometrial carcinomas and explore potential associations with patient characteristics and clinical outcomes. Out of 58 patients with comprehensive follow-up data, a subgroup of 21 cases underwent rigorous IHC evaluation, involving estrogen receptor (ER), progesterone receptor (PR), Ki67, MLH1, MSH2, MSH6, PMS2, and p53 markers. Statistical analysis, employing the chi-squared test, was conducted to assess the connection between individual IHC markers and clinical outcomes, with particular emphasis on the influence of radiation, chemotherapy, or brachytherapy treatment, as well as the occurrence of recurrence or mortality. Notably, significant correlations were observed in cases where MSH2 and MSH6 exhibited positive results, indicating their association with the use of chemotherapy and brachytherapy. However, the analysis pertaining to International Federation of Gynecology and Obstetrics (FIGO) stage or tumor grade did not reveal any statistically significant relationships with these parameters.

Corresponding author: Maria Victoria Olinca, Associate Professor, MD, PhD; e-mail: maria.olinca@umfcd.ro

Abstract   Open Paper   Download PDF

5. NGS mutational status on first diagnostic tissue, liquid biopsy and mastectomy in G2-G3 breast cancer

Carmen Maria Ardeleanu, Maria Victoria Olinca, Cristian Gabriel Viisoreanu, Horatiu Alin Muresan, Adriana Tecuceanu-Vulpe, Georgiana Manole, Iulia Elena Gune, Bianca Galateanu, Andreea-Corina Ilie-Petrov, Flavia Ultimescu

Breast cancer is one of the more frequently diagnosed cancers leading to death in women, and, like other tumor types, it is heterogeneous in its immunophenotype. It harbors mutations that modify tumor aggressiveness, therapy responses, residual disease, drug resistance, and relapse rates in advanced stages. This study aims to assess the mutational status of G2 and G3 tumors using next-generation sequencing (NGS) on initial tissue biopsies, liquid biopsies, and mastectomy specimens. The histopathological (HP) diagnosis for the 32 selected cases was established via Hematoxylin-Eosin (HE) staining by two observers. For the immunohistochemical (IHC) testing of estrogen receptor (ER), progesterone receptor (PGR) and human epidermal growth factor receptor 2 (HER2), we used the Ventana BenchMark Ultra. Ki67 testing was conducted using Bond-III from Leica. For cases with a score of 2+, gene amplification was assessed by silver-enhanced in situ hybridization (ISH) (SISH; Inform HER2 Dual ISH) on Ventana BenchMark Ultra. NGS analysis was initially performed on biopsies and plasma, and later on mastectomy specimens. After automated deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) extraction, concentrations were measured using the Invitrogen Qubit system. Libraries were created using Oncomine systems, and sequencing and analysis were done with the Ion Torrent system. Most tumors were graded as G3 (19 cases), with Luminal A being the predominant molecular subtype, and a significant number displayed HER2/HER2-low characteristics (24 out of 32 cases). The NGS assessment showed that phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations were the most frequent across all sample types. A significant limitation was the high number of invalid plasma tests due to pre-analytical handling errors or transport issues. Nonetheless, plasma testing (liquid biopsy) proved useful for monitoring tumor evolution and assessing residual disease.

Corresponding author: Andreea-Corina Ilie-Petrov, MD; e-mail: andreea.petrov@drd.umfcd.ro

Abstract   Open Paper   Download PDF

6. Classic and molecular cytogenetic findings in leukemia patients from the Western part of Romania

Cristina Annemari Popa, Nicoleta Ioana Andreescu, Teodora Smaranda Arghirescu, Carmen Angela Maria Petrescu, Cristian Marius Jinca, Emil Florin Hut, Razvan Gabriel Dragoi, George Puenea, Daniel Popa

Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in childhood and rare in adults, while acute myeloid leukemia (AML) is less common in children and more common in older adults. The aim of the study was to present our experience for the diagnostic of leukemia by using the classic and molecular cytogenetic methods. The study was conducted between 2009 and 2019 within the Classic and Molecular Genetic Laboratory of the Oncohematology Department from the Louis Turcanu Emergency Hospital for Children, Timisoara, Romania. The study group included 337 children and adults, evaluated between 2009 and 2019. By using the conventional and molecular cytogenetic technique, the cytogenetic anomalies found were 35 numerical chromosomal abnormalities, 10 (9;22)(q34;q11) [four ALL, one AML, five chronic myeloid leukemia (CML)] translocations, nine (15;17)(q24;q21) translocations, three (14;14)(q11;q32) translocations, two (4;11)(q21;q23) translocations, one (1;14)(p32;q11) translocation, one (7;14)(qter;q11) translocation, one (8;21)(q22;q22) translocation, one (9;14)(p12;q32) translocation, seven rearrangements of the MLL gene and two rearrangements of the core-binding factor subunit beta/myosin heavy chain 11 (CBFB/MYH11) gene. The use of conventional and molecular cytogenetic analysis is one of the most important prognostic indicators in acute leukemia patients, allowing the identification of biologically distinct subtypes of disease and selection of appropriate treatment approaches.

Corresponding author: Nicoleta Ioana Andreescu, MD, PhD; e-mail: nicollandreescu@yahoo.com; Teodora Smaranda Arghirescu, MD, PhD; e-mail: sarghirescu@yahoo.com

Abstract   Open Paper   Download PDF

7. Triple-negative breast cancer: from classical clinicopathological features to androgen receptor profile

Iulian Prutianu, Simona Eliza Giusca, Bogdan Gafton, Mariana Bianca Chifu, Cristina Terinte, Alexandra Antonescu, Larisa Popovici, Irina-Draga Caruntu

Triple-negative breast cancer (BC) represents an extensively analyzed entity to establish the overall framework of clinicopathological characteristics, with an impact on defining prognostic and predictive factors. The relationship between triple-negative BC and androgen receptor (AR) is far from being clarified. We aimed to evaluate the classical clinicopathological spectrum that characterized a triple-negative BC, focusing on AR expression. The study group comprised 124 cases of triple-negative BC. The main clinicopathological parameters were extracted from medical records. The immunohistochemical (IHC) exam was run using the following antibodies: anti-estrogen receptor (ER), anti-progesterone receptor (PR), anti-human epidermal growth factor receptor (HER2/neu), anti-Ki67 and anti-AR. AR immunoexpression was assessed as absent (completely negative) or present (unrelated to percentages and intensity). Data were statistically analyzed. AR expression was positive in 78 (63%) cases and negative in 46 (37%) cases. Among the study group, 28 cases exhibited an AR percentage ranging from 1% to 10%, 15 cases showed a percentage between 11% and 50%, while 12 cases had AR values between 51% and 75% and 23 cases fell within the AR range of 76% to 100%. No significant differences between AR immunoexpression (negative versus positive), clinicopathological characteristics and survival parameters were found. Statistically significant differences were registered between histological type, tumor stage, distant metastasis, tumor-infiltrating lymphocytes (TILs), treatment and residual cancer burden (RCB), and survival parameters. Thus, our results sustain that AR does not affect the biological behavior of triple-negative BC.

Corresponding author: Simona Eliza Giusca, Associate Professor, MD, PhD; e-mail: simonaelizagiusca@gmail.com; Mariana Bianca Chifu, Assistant Professor, MD, PhD; e-mail: bianca.manole@ymail.com

Abstract   Open Paper   Download PDF

8. The therapeutic benefits of NSAIDs and physical therapy in knee osteoarthritis

George Ovidiu Cioroianu, Alesandra Florescu, Cristiana Eugenia Simionescu, Teodor Nicusor Sas, Danut Nicolae Tarnita, Otilia Constantina Rogoveanu

Introduction: Osteoarthritis (OA) has been established as a progressive wear and tear disease of the synovial joints, which also involves a certain degree of inflammation. Considering there is no disease modifying medication available at the moment, the current guidelines focus on the symptomatic treatment of the affection. Our study aimed to evaluate the therapeutic advantages of the synergistic use of non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy in the treatment of knee osteoarthritis (KOA). Patients, Materials and Methods: The study comprised 46 individuals who were diagnosed with KOA and were admitted to the Department of Physical Medicine and Rehabilitation at the Emergency Clinical County Hospital of Craiova, Romania, between January 2021 and April 2022. All the participants received the same combination of pharmacological (Diclofenac 150 mg/day, no more than 10 days/month as needed) and non-pharmacological treatment (a 24-week plan of physical therapy). Results: The patient group exhibited a statistically significant reduction in both the average Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index (p=0.0142) and the average Visual Analog Scale (VAS) (p=0.0023). Additionally, there was a statistically significant increase in both the average Knee Outcome Survey-Activities of Daily Living (KOS-ADL) (p=0.0128) and the average Oxford Knee Score (OKS) (p=0.0023). The study found a significant positive correlation between higher VAS ratings and cholesterol levels (p=0.0092), but no significant correlation between VAS scores and triglyceride levels (p=0.0986). Patients were evaluated for a further 24 weeks beyond the conclusion of the research to see if surgical intervention was necessary during this time. Conclusions: Our investigation tracked the WOMAC, VAS, KOS-ADL, and OKS measurements in a cohort of patients with KOA. The results demonstrate that the utilization of NSAIDs in conjunction with physical therapy effectively alleviates pain and enhances joint functionality.

Corresponding author: Alesandra Florescu, Assistant Professor, MD, PhD; e-mail: alesandra.florescu@umfcv.ro

Abstract   Open Paper   Download PDF

9. A 10-year retrospective study of the risks and peculiarities in pediatric patients with (para)gonadal tumors and cysts

Usiwoma Okeroghene Ataikiru, Emil Radu Iacob, Elena Rodica Heredea, Maria Corina Stanciulescu, Mihai Codrin Galinescu, Calin Marius Popoiu, Eugen Sorin Boia

Introduction: Gonadal pediatric tumors are rare, ranking fourth (6%) among pediatric tumors, by Surveillance, Epidemiology, and End Results Program (https://seer.cancer.gov/). They have vague symptoms, leading to late discovery, but early detection and identifying its risk factors result in favorable prognosis and reduction of its incidence respectively. Patients, Material and Methods: A 10-year retrospective study identified peculiarities and risk factors in 210 children till age 17 with (para)gonadal tumors. Results: Stress, pollution (agricultural chemicals, insecticides and metal mine), obesity, breastfeeding <=5 months, malformations [mainly non-genetic related 67/87 (77%), especially eye malformation - 64%], hormone, smoking, positive heredo-genetic history, rural residence area, abnormal birth weight, and menstruation disorders showed an increased gonadal malignancy risk; relative risk ratio (RR): 1.33, 1.30, 1.34, 1.11, 1.65, 1.16, 1.36, 1.10, 1.00, 1.08 and 1.15 folds, respectively. RR for histopathological subtypes: immature teratoma (IT) (pollution - 1.75, Rhesus positive - 3.41), dysgerminoma (menstruation disorders - 2.80), granulosa cell tumor (stress - 2.10, menstruation disorders - 2.80), mucinous cystadenomas (obesity - 2.84, no postnatal vaccine - 3.71), mature teratomas (stress - 2.35, malformations - 2.18) and serous cystadenomas (breastfeeding <=5 months - 2.53), dependent variables being mixed germ cell tumors (GCTs) and cysts. Children presenting with bleeding (73%), abdominal distention (62%), elevated tumor markers (91%), (multilocular) solid tumor (88% and 100%), tumor size >10 cm (65%), GCTs (74%), death (100%), metastases (100%), viruses (77%), loss of appetite (68%), and weight (85%), had gonadal malignant tumors, especially mixed GCTs and IT. Conclusions: Avoiding these risk factors will prevent and reduce gonadal pediatric tumors. Investigating children presenting with the listed peculiarities, especially if exposed to the mentioned risk factors, will enable early gonadal tumor identification, successful patient management, and favorable prognosis.

Corresponding author: Emil Radu Iacob, Associate Professor, MD, PhD; e-mail: radueiacob@umft.ro, radueiacob@yahoo.com

Abstract   Open Paper   Download PDF

10. Automated cutaneous squamous cell carcinoma grading using deep learning with transfer learning

Alexandra Buruiana, Mircea-Sebastian Serbanescu, Bogdan Pop, Bogdan-Alexandru Gheban, Carmen Georgiu, Doinita Crisan, Maria Crisan

Introduction: Histological grading of cutaneous squamous cell carcinoma (cSCC) is crucial for prognosis and treatment decisions, but manual grading is subjective and time-consuming. Aim: This study aimed to develop and validate a deep learning (DL)-based model for automated cSCC grading, potentially improving diagnostic accuracy (ACC) and efficiency. Materials and Methods: Three deep neural networks (DNNs) with different architectures (AlexNet, GoogLeNet, ResNet-18) were trained using transfer learning on a dataset of 300 histopathological images of cSCC. The models were evaluated on their ACC, sensitivity (SN), specificity (SP), and area under the curve (AUC). Clinical validation was performed on 60 images, comparing the DNNs predictions with those of a panel of pathologists. Results: The models achieved high performance metrics (ACC>85%, SN>85%, SP>92%, AUC>97%) demonstrating their potential for objective and efficient cSCC grading. The high agreement between the DNNs and pathologists, as well as among different network architectures, further supports the reliability and ACC of the DL models. The top-performing models are publicly available, facilitating further research and potential clinical implementation. Conclusions: This study highlights the promising role of DL in enhancing cSCC diagnosis, ultimately improving patient care.

Corresponding author: Mircea-Sebastian Serbanescu, Associate Professor, MD, PhD; e-mail: mircea_serbanescu@yahoo.com

Abstract   Open Paper   Download PDF

11. Aortic aneurysms in patients with atherosclerotic coronary artery disease in the southwestern region of Romania - clinical and histopathological study

Diduta Alina Brie, Adelina Maria Jianu, Roxana Popescu, Teodor Cerbulescu, Sorin Dema, Daniel Miron Brie, Veronica Madalina Boruga

An aneurysm is defined as a dilation of the arterial wall with a diameter exceeding 1.5 times the normal diameter of the vessel concerned. Aortic aneurysms (AAs) can develop at any level but are mostly found at the abdominal and infrarenal levels and extend to the iliac arteries. AAs are usually asymptomatic and are most often discovered incidentally during various imaging investigations for other conditions. Rupture of an AA is usually dramatic, being one of the causes of sudden cardiac death. Surgical treatment and, more recently, endovascular treatment are the only effective methods of AA repair. In this study, we screened for the diagnosis of AAs in patients with stable exertional angina who had indications for coronary angiography. The study was carried out in the period 2021-2023 in the Institute of Cardiovascular Diseases Timisoara, Romania. Of the 2458 patients with exertional angina who required coronary angiography, a number of 1844 (75%) patients had at least one stenotic atheromatous plaque, and of these 312 patients had AAs, of which 173 at the level of the abdominal aorta.

Corresponding author: Daniel Miron Brie, MD, PhD; e-mail: brie_daniel@yahoo.com

Abstract   Open Paper   Download PDF

12. Implementing an integrated molecular classification for gastric cancer from endoscopic biopsies using on-slide tests

Simona Costache, Adelina Baltan, Sofia Diaz Mclynn, Mattia Pegoraro, Rebecca de Havilland, Matthew Porter, Ana Lerga, Teresa Thomas, Alina Elena Chefani, Sarah Wedden, Kim Billingham, Corrado D Arrigo

The availability of more effective biological therapy can improve outcomes of gastric cancer (GC), but most patients do not have access to personalized treatment. GC molecular classification helps identify patients suitable for specific therapies and provides useful prognostic information. To date, only a small number of patients have access to molecular classification. We proposed a working molecular classification that can be delivered using on-slide tests available in most histopathology laboratories. We used eight on-slide tests [in situ hybridization (ISH) for Epstein-Barr virus-encoded small ribonucleic acid (EBER) and immunohistochemistry (IHC) for MutL homolog 1 (MLH1), PMS1 homolog 2 (PMS2), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), E-cadherin, beta-catenin and p53] to classify GC into one of six categories: GC associated with Epstein-Barr virus (GC-EBV), GC mismatch repair deficient (GC-dMMR), GC with epithelial-mesenchymal transition (GC-EMT), GC with chromosomal instability (GC-CIN), GC genomically stable (GC-GS) and GC not otherwise specified (GC-NOS)/indeterminate. The classification has provision also for current and future on-slide companion diagnostic (CDx) tests necessary to select specific biological therapies and, as proof of principle, in this study we used three CDx tests currently required for the management of GC [human epidermal growth factor receptor 2 (Her2), programmed cell death-ligand 1 (PD-L1) 22C3 and Claudin18.2 (CLDN18.2)]. This paper describes the necessary tissue pathways and laboratory workflow and assesses the feasibility of using this classification prospectively on small endoscopic biopsies of gastric and gastroesophageal junction adenocarcinoma. This work demonstrates that such molecular classification can be implemented in the context of a histopathology diagnostic routine with little impact on turnaround times and laboratory capacity. The widespread adoption of a molecular classification for GC will help refine prognosis and guide the choice of more appropriate biological therapy for these patients.

Corresponding author: Simona Costache, MD, PhD Student; e-mail: simona.costache.anapat@gmail.com

Abstract   Open Paper   Download PDF

13. The expression of c-MYC, Cyclin D1 and Ki-67/MIB-1 in benign and malignant thyroid tissues: is there any diagnostic value?

Evropi Forozidou, Antonia Syrnioti, Styliani Laskou, Alexandros Poutoglidis, Konstantinos Sapalidis, Triantafyllia Koletsa

Aim: To investigate the immunohistochemical (IHC) expression and the diagnostic value of c-MYC, Cyclin D1, and Ki-67/MIB-1 in follicular adenomas (FAs), follicular carcinomas (FCs), and anaplastic carcinomas (ACs) of the thyroid gland, as well as in their corresponding adjacent, non-neoplastic thyroid tissue (NNTT). Materials and Methods: We conducted a retrospective study of patients who were pathologically diagnosed with FA, FC, or AC after total thyroidectomy. Tissue microarrays with cores taken from neoplastic and adjacent NNTT were constructed. Immunohistochemistry for anti-c-MYC, anti-Cyclin D1, and anti-Ki-67/MIB-1 antibodies was performed, and the positivity was evaluated. Results: Twenty-eight specimens were included. Nuclear c-MYC positivity was observed in 4/11 FCs, and 3/4 ACs, whereas cytoplasmic c-MYC positivity was found in 16/24 NNTTs. Globally, there were statistically significant differences between neoplasms and NNTTs, with higher nuclear c-MYC and Cyclin D1 expression observed in neoplasms (p=0.017 and p=0.001, respectively). In contrast, cytoplasmic positivity was seen solely in NNTTs (p=0.001). Cyclin D1 positivity was noted in 11/13 FAs, 7/11 FCs, 2/4 ATCs, and only in one NNTT. A statistically significant correlation was found between MIB1 and c-MYC nuclear positivity (p=0.040). Conclusions: Our findings exhibit a clear difference in the IHC expression of c-MYC and Cyclin D1 between different types of thyroid tumors, as well as between the neoplastic and NNTT. Nuclear c-MYC positivity excludes the benign nature of a thyroid lesion, in contrast to cytoplasmic positivity, which demonstrates normal or hyperplastic nature.

Corresponding author: Alexandros Poutoglidis, MD, PhD; e-mail: xilouris21@gmail.com

Abstract   Open Paper   Download PDF

14. The particularities of connective fibers from the wall of varicose veins extirpated by cryostripping

Andrei Florin Parau, Amalia Raluca Ceausu, Nela Pusa Gaje, Sorin Olariu, Marius Raica

Introduction: The varicose vein affects more than 30% of the general population. Significantly increased rates were noticed in women and older population. From the histopathological point of view, venous arterialization, smooth muscle cell hypertrophy, and hyperplasia are the main changes noticed in varicose vein disease. Some of the main therapeutic methods used in the management of varicose disease are injection sclerotherapy, conservative, surgical, saphenous vein inversion and removal, high saphenous ligation, ambulatory phlebectomy, transilluminated powered phlebectomy, endovascular management, cryostripping. Aim: The aim of this study was to evaluate the morphology of connective fibers from the wall of the varicose veins extirpated by cryostripping. Patients, Materials and Methods: The study included 109 samples taken by cryostripping method. Hematoxylin-Eosin, Masson s trichrome, Silver and Orcein staining were applied. The assessment of fibers was made according to score values between 0 and 3. Results: It was found no major structural differences in terms of alterations of collagen fibers induced by the applied surgical procedure. It was noticed duplications and multiplications of the internal elastic lamina, as diffuse and nodular forms. Depletion of elastic fibers at the media was a lesion identified in most of the specimens. The depletion of reticulin fibers correlates with the accumulation of collagen fibers, which partially or completely replace the network in the media and intima. No correlation was found between changes in the reticulin network and the time between prelevation and buffered formalin fixation, the maximum time investigated being five days. Conclusions: The Orcein staining in the venous vessel evaluation panel may be a useful investigation.

Corresponding author: Nela Pusa Gaje, Associate Professor, MD, PhD; e-mail: gaje.nela@umft.ro

Abstract   Open Paper   Download PDF

15. Abrasion and dental pulp morphological changes in occlusal dysfunction

Adi Rusu Olaru, Mihai Raul Popescu, Iancu Emil Plesea, Mircea-Sebastian Serbanescu, Razvan Mihail Plesea, Melania Olimpia Cojocaru, Elena-Claudia Coculescu

Aim: The authors set out to assess if the presence and the degree of severity of the abrasion, as a consequence of the occlusal dysfunction, determine further morphological changes in the dental pulp. Materials and Methods: Study group included teeth dental pulp from 45 cases with occlusal dysfunction, subsequently divided into two subgroups: 24 cases with abrasion (AB) and 21 cases without abrasion (NONAB). The set of morphological parameters of dental pulp were thicknesses of the outer layer, inner layer and entire peripheral pulp zone, the presence of pulpal calcifications and their extent within the dental pulp, the presence of interstitial fibrosis and its extent within the dental pulp and the vascular density (VD) of pulpal capillary network. Tissue samples were fixed in 10% buffered formalin, embedded in paraffin, and sectioned off at 4 micrometers. Serial slides were stained with Hematoxylin-Eosin (HE), Masson s trichrome (MT) and anti-cluster of differentiation 34 (CD34) antibodies labeled with 3,3-Diaminobenzidine (DAB) and transformed into virtual slides on which the above-mentioned parameters were studied comparatively with the help of a dedicated in-house software, realized in MATLAB (MathWorks, USA). The numerical values of the assessed parameters were also stratified in classes, thus obtaining score scales for each parameter. Statistical tools used were Lilliefors test, t-test (two-sample assuming equal variances), Mann-Whitney test, Pearson s correlation test, one-way analysis of variance (ANOVA) test and chi-squared test. Results and Discussions: Both peripheral zone (PZ) and its layers individually tended to be thicker in the teeth with abrasion than in those without abrasion. Also, teeth with abrasion tended to develop larger amounts of calcium deposits in their dental pulp than teeth without abrasion. On the other hand, fibrotic tissue in dental pulp had no relationship with the presence or absence of abrasion. PZ as a whole and its layers evolved together in the same way, with a stronger correlation in the group of teeth without abrasion. Deposits of calcium evolved in the opposite direction to both the amount of fibrous tissue and the capillaries density of the dental pulp. Consequently, the amount of fibrous tissue and VD evolved together in the same way, more pronounced in the teeth without abrasion. Conclusions: Our preliminary study pointed out that different components of the dental pulp showed slight to moderate changes depending on the degree of abrasion in teeth with occlusal dysfunction.

Corresponding author: Mihai Raul Popescu, Professor, MD, PhD; e-mail: popescumihairaul@yahoo.com

Abstract   Open Paper   Download PDF

16. Fatty infiltration and ventricular premature beats originating from right ventricular outflow tract: association or causality?

Raluca-Vasilica Sirbu Prisecaru, Leila Riahi, Madalina Abagiu, Oana-Elena Purcar, Mircea-Corvin-Claudiu Vladoianu, Cristina Gabriela Leatu, Alexandru Dan Sirbu, Ioan Manitiu

Background: Anatomical evidence reveals heterogeneous fat distribution in both atrial and ventricular myocardium that are considered normal, but at the same time arrhythmogenic, and numerous cardiac pathophysiological conditions are associated with myocardial fat deposits. The relationship between fatty infiltration, especially in the epicardial layer and its pathophysiological implication is not completely understood. Aim: The aim of this study was to establish a positive or negative relationship between the ventricular burden and several parameters related to right ventricle (RV) adipose tissue - the RV thickness, RV indexed mass, body mass index (BMI), age, gender. Patients, Materials and Methods: Twenty-three patients with documented premature ventricular contractions (PVCs) originating from right ventricular outflow tract based on electrocardiography (ECG) evaluation were hospitalized between January 2018-November 2022 for electrophysiological study and PVCs ablation. Data obtained after collecting the clinical characteristics, ECG, RV measurements from transthoracic echocardiography (TTE), cardiac computed tomography (CT) and magnetic resonance imaging (MRI) were analyzed. Results: A weak positive relationship between the ventricular burden and BMI (r=0.14, p=0.49), tricuspid annular plane systolic excursion (TAPSE) (r=0.07, p=0.7), the RV thickness (r=0.03, p=0.8), epicardial adipose tissue (r=0.13, p=0.55), RV mass indexed (r=0.05, p=0.82) was observed. No clear cut-off of the PVCs burden could be established in terms related to the increase in BMI, RV thickness, epicardial adipose tissue, RV mass indexed. Conclusions: No significant positive or negative relationship between the ventricular burden and the RV thickness, RV indexed mass were found in individuals with a high PVCs originating from right ventricular outflow tract (RVOT) burden.

Corresponding author: Raluca-Vasilica Sirbu Prisecaru, MD, PhD Student; e-mail: raluvsirbu@gmail.com

Abstract   Open Paper   Download PDF

17. Modifications of the articular eminence inclination in association with the loss of occlusal support in the molar area. A cone-beam computed tomography study

Maria Justina Roxana Virlan, Victor Nimigean, Diana Loreta Paun, Adriana Bisoc, Vanda Roxana Nimigean

The articular eminence (AE) is part of the temporal component of the temporomandibular joint (TMJ). The inclination of the AE (AEI) has an important role in TMJ biodynamics, influencing the path of movement of the disc-condyle complex. Although AEI values might change due to tooth loss, little is known about what effect could have the loss of occlusal support in the molar area on AE morphology. AEI was measured on cone-beam computed tomography (CBCT) images of 41 patients (82 TMJs) with or without occlusal support in the molar region. The patients included in this study were divided into four groups: (1) patients with maintained occlusal support in the molar areas on both sides (right and left side) (MM); (2) patients with loss of occlusal support in the molar areas on both sides (right and left side) (LL); (3) patients with loss of occlusal support in the molar area only on the right side, but with maintained occlusal support on the left molar area (LM); (4) patients with loss of occlusal support in the molar area only on the left side, but with maintained occlusal support in the right molar area (ML). AEI values were higher in the TMJs on the side with maintained occlusal support in the molar area (M) than the AEI values measured in TMJs from the side with loss of occlusal support in the molar area (L). AEI values on the right side were higher in the MM patients in comparison to the AEI values on the right side of LL patients. The loss of occlusal support in the molar areas changes the mandibular biodynamics, which might be reflected in the morphological changes at the AE level, where it might cause flattening of the articular slope predominantly on the right side.

Corresponding author: Victor Nimigean, Professor, DMD, MD, PhD; e-mail: victor.nimigean@umfcd.ro; Diana Loreta Paun, Associate Professor, MD, PhD; e-mail: diana.paun@umfcd.ro

Abstract   Open Paper   Download PDF

18. Synchronous laryngeal cancer

Mircea Sorin Ciolofan, Florin Anghelina, Alexandru Nicolae Vlaescu, Mihaela Roxana Mitroi, Alina Nicoleta Capitanescu, Elena Ionita, Iulica Ionita, Nina Ionovici, Daniela Vrinceanu, Carmen Aurelia Mogoanta

Multiple primary cancers are usually defined as primary malignant tumors of different histological origins in one person. Synchronous cancers are defined as two or more primary cancers diagnosed in the same patient at the same time or within six months after identifying the first tumor, and those cancers that develop at more than a six-month interval are termed as metachronous multiple primary cancers. Our study comprised of a patient with synchronous laryngeal cancer with double localizations. The case was solved through surgical excision of the tumors. Histopathological and immunohistochemistry examinations revealed synchronous laryngeal cancer. Laryngeal cancer should usually be managed through surgical resection, followed by oncological treatment.

Corresponding author: Alexandru Nicolae Vlaescu, MD, PhD; e-mail: alex.vlaescu@gmail.com

Abstract   Open Paper   Download PDF

19. Orthodontic treatment of a non-syndromic patient with congenital agenesis of multiple permanent teeth: a rare case

Oana Cella Andrei, Mirela Ileana Dinescu, Adriana Bisoc, Daniela Ioana Tarlungeanu, Ruxandra Margarit, Magdalena Natalia Dina

This article presents the first stage of treatment, respectively the orthodontic management of a non-syndromic, 13-year-old patient, with multiple and asymmetric missing teeth. The difficulty of the case was increased by the association of an impacted premolar and also by the loss, due to extended caries, of three of the first permanent molars. The patient came from a rural area, where access to dental treatment was limited. His parents realized too late that the child had significant damage to his permanent first molars, that he was no longer eating properly and that he had spaces between teeth. The uncertain outcome of endodontic treatment and prosthetic restoration at the level of first permanent molars and the additional costs made the parents decide, together with the dental practitioner, to extract teeth Nos. 16, 36 and 46. Giving the situation, the first phase treatment plan was represented by orthodontic closing of several maxillary spaces and the reduction of edentulous ridge in the mandible, followed by the maintenance of the space for two future implants, each one replacing the first molars in the third and fourth quadrants. Particularly for this growing patient, early intervention to treat and save as much from the permanent teeth as possible, to expose the impacted premolar, to level and align the teeth in order to obtain continuous dental arches and a good occlusion plane, and later to apply space maintainers that will be replaced by prosthetic restorations, represented an enormous step for long-term stability and proper functioning.

Corresponding author: Adriana Bisoc, Lecturer, DMD, PhD; e-mail: adry_bis@yahoo.com; Daniela Ioana Tarlungeanu, Assistant Professor, DMD, PhD; e-mail: ioanatarlungeanu@gmail.com

Abstract   Open Paper   Download PDF

20. High-grade serous ovarian cancer (HGSOC) with fallopian tube involvement

Adina Elena Tanase, Iustina Petra Solomon-Condriuc, Raluca Anamaria Mogos, Gabriel Costachescu, Cristina David, Catalin Mihai Buzduga, Dragos Viorel Scripcariu, Claudia Florida Costea, Andrei Ionut Cucu, Gabriel Valentin Tanase, Daniela Maria Tanase, Dragos Nemescu, Ana Maria Dumitrescu, Alexandru Carauleanu

Introduction: Literature data present new studies about precancerous lesions of pelvic serous carcinoma that originate from the tubal secretory cells. It has long been thought that ovarian cancer cannot be prevented by prophylactic screening or surgery. In recent years, gynecologists have adapted to new principles and so, during routine hysterectomies in perimenopausal women for benign uterine pathologies, salpingo-oophorectomy is performed as a prophylactic approach. Aim: The purpose of our article was to draw attention to the association between abnormal fallopian tube pathology and the presence of serous ovarian neoplasia in perimenopausal women at risk. Case presentation: We report the case of a 45-year-old woman who had unspecific symptoms of abdominal pain and loss of appetite and weight. A pelvic magnetic resonance imaging was performed, and an ovarian mass was detected. Our case shows that the fallopian tube can be the primary point of origin for a pelvic disease, therefore prevention is possible with early computed tomography scan and annual ultrasound. The patient presented with a T1c staging post-surgery and her chances of survival could have decreased if she had postponed medical examination longer. We found a significant increase in the absolute number of tubal secretory cells in patients with ovarian neoplasia, which supports the assumption that serous tubal intraepithelial carcinoma lesions are found especially in the serous ovarian type. Conclusions: Our article is a strong suggestion that serous ovarian cancer originates from the fallopian tube and can potentially serve as a sensitive biomarker for early serous carcinogenesis within the fallopian tube.

Corresponding author: Catalin Mihai Buzduga, Lecturer, MD, PhD; e-mail: buzdugacatalin@yahoo.com; Claudia Florida Costea, Professor, MD, PhD; e-mail: costea10@yahoo.com

Abstract   Open Paper   Download PDF

21. Successfully physical therapy program for functional respiratory rehabilitation after lung transplant surgery - case report

Diana-Lidia Tache-Codreanu, Iuliana David, Cristiana Gabriela Popp, Lucian Bobocea, Magdalena Rodica Traistaru

The first lung transplant (LT) was made in Romania in 2018 at a 36-year-old male patient with chronic obstructive pulmonary disease (COPD). The study follows the first LT rehabilitation by describing the physical therapy program (PTP), the measurements of body mass and appendicular skeletal muscle mass (ASM) by bio-impedancemetry analysis (BIA) and the functional capacity assessment realized by the six-minute walk test (6MWT) and by the functional respiratory tests (FRTs) in order to evaluate the effectiveness of functional respiratory rehabilitation in this case during a period of one year. In parallel, repeated transbronchial biopsies were performed after six weeks, three months, six months and one year since the transplant. Only the first biopsies showed injuries suggesting an acute rejection, all the rest revealing mild, unspecific lesions. The patient followed 15 sessions of respiratory exercises, joints mobilizations and progressive global muscle strength started one month after LT surgery and was also instructed to perform the exercises at home, using a tablet given at discharge and under monthly guidance through telemedicine. All the measurements were performed before and after the rehabilitation cure, and it was repeated at three different evaluations for one year. The results showed that at the end of follow-up, the 6MWT was significantly increased from 59% of predicted distance at the intake in post-acute hospitalization to 166% at one year after LT, without desaturation that represent a very good evolution; the FRTs increased to normal, and the body weight increased with 18 kg (from severe underweight to normal weight) with constant increasement of skeletal muscle mass. The use of PTP after LT surgery significantly improves functional capacity and increases body mass and skeletal muscle mass.

Corresponding author: Cristiana Gabriela Popp, MD; e-mail: brigaela@yahoo.com

Abstract   Open Paper   Download PDF

22. Eosinophilic fasciitis: unraveling the clinical tapestry of a rare case and review of literature

Aifer Cherim, Alexandra Eugenia Bastian, Cristiana Gabriela Popp, Maia Ioana Mihon, Ion Cristian Efrem, Ananu Florentin Vreju, Razvan Adrian Ionescu

Eosinophilic fasciitis (EF) remains a diagnostic challenge due to its rarity and resemblance to scleroderma. This case report aims to provide a cohesive exploration of EF s clinical nuances, emphasizing the importance of accurate diagnosis and effective management. A 52-year-old male developed bilateral forearm and calf hardening, along with erythema, pruritus, and pain four months prior to the presentation in our Clinic. The symptoms initially debuted bilaterally in the forearms and progressed to involve the calves, distal arms, and thighs. Clinical examination revealed symmetrical plaques on forearms and calves, featuring erythematous, hyper, and hypopigmented elements extending proximally, a positive groove sign and a moderate difficulty in knee joint flexion. Despite these findings, the patient was generally in good condition, without any other notable clinical signs. Initial laboratory findings showed slightly increased percentual eosinophil levels, elevated C-reactive protein (CRP), normal erythrocyte sedimentation rate (ESR), and negative antinuclear and scleroderma specific antibodies. Magnetic resonance imaging (MRI) demonstrated enhanced fascial signal and thickening while the fascia-muscle biopsy revealed marked edema and inflammatory lymphoplasmacytic infiltrate, consistent with the diagnosis of EF. The patient showed a favorable response to systemic corticosteroids. EF predominantly affects males aged 30 to 60 and is characterized by a sudden onset and unclear etiological factors. Differential diagnosis requires careful exclusion of scleroderma and other mimicking conditions. Diagnostic modalities such as skin-muscle biopsy and MRI reveal characteristic findings like inflammatory infiltrate and fascial thickening. Accurate diagnosis and differentiation from scleroderma are crucial, with early intervention involving glucocorticoids and immunosuppressive agents improving long-term outcomes.

Corresponding author: Ion Cristian Efrem, Associate Professor, MD, PhD; e-mail: cristian.efrem@umfcv.ro, ic_efrem@yahoo.com

Abstract   Open Paper   Download PDF

23. Post-traumatic avascular necrosis of the talus

Paul Alexandru Deme, Dan Ioan Fruja, Nicolae Catalin Hreniuc, Gratian Cosmin Damian, Florin Mihai Marcu, Roland Fazakas, Casiana Boru, Nicoleta Zurbau-Anghel, Alexandru Mircea Pop

In this comprehensive case report, we examine a 29-year-old male who suffered a high-energy vehicular accident, resulting in a type III Hawkins fracture of the talus. This specific fracture type is critically associated with a greater than 90% risk of progressing to avascular necrosis (AVN) of the talus, a severe and debilitating condition. Alongside this, the patient sustained fractures of the medial and lateral malleolus. Due to extensive swelling and severe circulatory disorders, an immediate emergency surgical procedure was necessitated, employing nail fixation as a stabilizing intervention. Over the course of 12 months following the surgery, despite routine post-operative imaging including X-rays and computed tomography (CT) scans, the patient continued to experience significant pain and impairment. This condition led to further investigations, culminating in a magnetic resonance imaging (MRI) that revealed an area of 19.8/20.9 mm of AVN on the talus dome s upper-lateral facet. Interestingly, earlier CT scans had indicated multiple osteitic lesions, but these findings lacked a clear clinical correspondence, presenting a diagnostic challenge. To resolve this ambiguity and to definitively distinguish between necrosis and infection, a targeted histopathological analysis was deemed necessary. This analysis was conducted on a bone fragment extracted during a follow-up surgical procedure for nail removal. The results from this analysis present an area of bone and myeloid tissue necrosis unequivocally confirming the presence of AVN, effectively ruling out osteitis as a potential diagnosis. This critical diagnostic clarification allowed for a shift in therapeutic strategy, enabling the initiation of a more focused and potentially curative treatment regimen.

Corresponding author: Paul Alexandru Deme, Assistant Professor, MD, PhD Student; e-mail: demepaul@gmail.com

Abstract   Open Paper   Download PDF

24. From morphology of human body to reshaping a morphology of the society: heritage in the field of pathology of infectious diseases of Wilhelm Ebstein and work of councilman Sigismund Asch. A story how to counteract epidemics and to transform feudal system into civil democracy

Andrzej Wincewicz, Piotr Woltanowski

Collected, primary resources enabled us to extract data that are scarcely present in medical literature of the two Breslauer morphologists of both the human body and - metaphorically - the society: Wilhelm Ebstein (1836-1912) and Sigismund Asch (1825-1901), particularly the latter, who described morphology of melanosis in his doctoral dissertation in 1846, to switch on reshaping social morphology of Wroclaw (Breslau) in Virchow-like manner. In contrast to the main perspective of Ebstein s anomaly that has been finely described in past biographical papers, a primary aspect of infectious diseases is highlighted here in Ebstein s heritage. In 1869, his habilitation on recurrent typhus provided professional support for Asch. As Ebstein cared for the poor in shelters of Wroclaw, Asch admitted poor patients from early morning hours to gain such a great esteem to be elected alderman. Asch s mentality corresponded to Ferdinand Lassalle s philosophy of the social democratic movement. In front of cholera epidemics, Asch contributed to medical control of meat, development of city canalization, establishment of green areas as well he deeply got involved in charity institutions for widows and orphans and was a model medical doctor to follow for much more famous Janusz Korczak who perished together with children from his orphanage in Nazi Concentration Camp in Treblinka. Asch was immortalized as Doctor Klaus in the popular play by Adolf L Arronge and united people in progress from feudal discrimination to democracy and in fight for civil rights in industrial society to gradually replace aristocracy with meritocracy in the mainstream of development of modern society.

Corresponding author: Andrzej Wincewicz, Associate Professor, MD, PhD; e-mail: ruahpolin@yahoo.com, andwinc@gmail.com

Abstract   Open Paper   Download PDF
Download cover
Download contents

Journal archive