Expression of Calcitonin Gene-Related Peptide and Calcitonin Receptor-like Receptor in Colorectal Adenocarcinoma.

Colorectal cancer is one of the most widespread types of cancer that still causes many deaths worldwide. The development of new diagnostic and prognostic markers, as well as new therapeutic methods, is necessary. The calcitonin gene-related peptide (CGRP) neuropeptide alongside its receptor calcitonin receptor-like receptor (CRLR) could represent future biomarkers and a potential therapeutic target. Increased levels of CGRP have been demonstrated in thyroid, prostate, lung, and breast cancers and may also have a role in colorectal cancer. At the tumor level, it acts through different mechanisms, such as the angiogenesis, migration, and proliferation of tumor cells. The aim of this study was to measure the level of CGRP in colorectal cancer patients' serum by enzyme-linked immunosorbent assay (ELISA) and determine the level of CGRP and CRLR at the tumor level after histopathological (HP) and immunohistochemical (IHC) analysis, and then to correlate them with the TNM stage and with different tumoral characteristics. A total of 54 patients with newly diagnosed colorectal adenocarcinoma were evaluated. We showed that serum levels of CGRP, as well as CGRP and CRLR tumor level expression, correlate with the TNM stage, with local tumor extension, the presence of lymph node metastasis, and distant metastasis, and also with the tumor differentiation degree. CGRP is present in colorectal cancer from the incipient TNM stage, with levels increasing with the stage, and can be used as a diagnostic and prognostic marker and may also represent a potentially new therapeutic target.

Associations of Ultrasound Findings with Serum Iron and Ferritin Levels in Children with Obesity.

The nutritional status of children is always a concern for medical professionals. Increasingly, obesogenic factors have created a new global epidemic. Obesity is characterized by persistent inflammation, which can have detrimental effects on the growth and development of children. Iron and ferritin are both important factors to consider when evaluating these children due to their role in the pathophysiology of chronic inflammation. Recently, ultrasonographic evaluation seems to be an increasingly used method in pediatric clinical practice. In this study, we included 98 children aged 6-14 years, 72 of whom were obese and 26 had normal weight. The data obtained indicated that there was an association between low iron and increased ferritin levels, aspects of non-alcoholic fatty liver visualized by ultrasonography, and the degree of fibrosis assessed elastographically. Ultrasonography can help us identify liver damage, but the possibility of identifying an association with other paraclinical investigations such as iron and ferritin levels can be cumulative. In this way, the assessment can be more complex, as the child benefits from comprehensive evaluation and management. The results drew attention to non-invasive, easy-to-perform, and low-cost methods of assessing obese children in terms of iron metabolism and structural liver changes.

C-Reactive Protein as a Marker of Inflammation in Children and Adolescents with Metabolic Syndrome: A Systematic Review and Meta-Analysis.

Metabolic syndrome (MetS) in the pediatric population has been reported in many studies to be associated with an inflammatory response. However, to our knowledge, there is no definitive conclusion in the form of a meta-analysis. The issue we aimed to address is whether C-reactive protein (CRP) is a trustworthy marker in detecting inflammation in children and adolescents with MetS. We systematically searched PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, the ISI Web of Science, and SCOPUS until 31 June 2023 for studies involving children and adolescents with MetS where hsCRP or CRP were measured. After the screening process, we identified 24 full-text articles that compared 930 patients with MetS with either healthy (n = 3782) or obese (n = 1658) controls. The risk of bias in the included studies was assessed using the Begg's rank correlation test and Egger's regression test. Statistical analysis was carried out based on pooled mean differences (MDs) and an associated 95% CI. Data analysis showed that MetS is associated with higher levels of CRP than those in healthy controls (MD = 1.28, 95% CI: (0.49-2.08), p = 0.002) in obese patients (MD = 0.88, 95% CI: (0.38-1.39), p = 0.0006). However, conventional methods of CRP analysis were found to be more accurate in differentiating between children and adolescents with obesity and those with MetS, compared with hsCRP (MD = 0.60, 95% CI: (-0.08-1.28), p = 0.08). No risk of bias was assessed. In conclusion, CRP is a reliable inflammatory marker for differentiating pediatric patients with MetS from healthy ones. On the other hand, it did not prove to be very accurate in distinguishing between patients who had MetS and those who were obese. There should be more research performed in this field.

Immunoexpression of Claudins -3, -4 and -7 in prostate adenocarcinomas.

Claudins are a family of essential tight junction proteins, abnormally expressed in human carcinomas. The studies that indicated the involvement of claudins in tumor biology and progression suggest the possibility of their utility as markers for diagnosis or prognosis, but also as possible targets for therapy. We investigated 50 prostate adenocarcinomas (PAs) for which we followed the expression of Claudins -3, -4 and -7 in relation to International Society of Urological Pathology (ISUP) grades. We observed the positivity for Claudin-3, Claudin-4, and Claudin-7 in 76%, 74% and 46% of cases. Analysis of the immunoexpression pattern revealed the cytoplasmic and nuclear translocation for Claudins -3 and -4, and only cytoplasmic for Claudin-7. For all claudins investigated, we noted a final staining score with significantly higher values or at the limit of statistical significance for PA belonging to ISUP groups 1-4. The internalization of Claudins -3, -4 and -7 expression, regardless of the degree of PA, indicates their involvement in prostate carcinogenesis. In addition, the similar immunoexpression patterns of the three investigated claudins and their positive linear correlation suggest a coordinated regulation and indicate the possibility of a targeted treatment strategy.

The Role of Vitamin D in Obese Children with Non-Alcoholic Fatty Liver Disease and Associated Metabolic Syndrome.

Non-alcoholic fatty liver disease (NAFLD) represents a complex chronic condition, which in the absence of screening-monitoring markers and effective standardized treatment is one of the most important issues in pediatric pathology. In this study, we analyzed the role of vitamin D supplementation in obese children with/without NAFLD and the impact on the components of the associated metabolic syndrome (MS). The study included 22 children with simple obesity (SO) and 50 with NAFLD, aged between 6 and 14 years, who received regimen-based therapy or vitamin D supplementation in case of deficiency. Anthropometric and paraclinical data associated with MS were statistically compared before and after treatment. It was observed that there was a statistical association of NAFLD with MS components, which were present both in SO and in the 6-9 years group. Vitamin D deficiency was associated with the presence of obesity, NAFLD and MS components, and correction of the deficiency induced a tendency to normalize the associated parameters. In the case of a treatment strictly based on the regimen, we found decreases in vitamin D values and additional alteration of some parameters. Supplementation with vitamin D potentiates the effects of the specific regimen, and the effects seem to be dependent on the MS components.

Clinicopathological Prognostic Parameters of Endometrioid Endometrial Carcinomas.

Endometrioid endometrial carcinomas (EEC) are common malignant lesions of the female genital tract, with incidence and risk factors that raise issues to improve histopathological prognostic factors. The study included 50 EEC cases, for which the clinicopathological parameters represented by age, risk factors, tumor grade, histological differences, invasion pattern, tumor stage and association of endometrial hyperplasia were analyzed statistically. The results indicated the predominance of EEC in the 7th decade of life, with associated risk factors (78%), more frequently well differentiated (52%), with no other specifications related to differentiation (NOS, 60%), with irregular invasion pattern (66%) in<50% of the myometrial wall (48%). Irregular pattern, microcystic, elongated, and fragmented (MELF) pattern and myoinvasion associated with vascular invasion (MVI) pattern were significantly associated with high grade and advanced stage tumors. With the exception of EEC-NOS and squamous differentiation, all other tumors were associated with low grade (G1). In this study there was a tendency to associate the age group of 60-69 years with the presence of endometrial hyperplasia and with high grade and advanced stage. Apart from the high grade and advanced stage, in the aggressive profile of the EEC can be included as the clinicopathological parameters the 7th decade of life and the irregular, MELF and MVI invasion patterns.

The analysis of hormonal status and vascular and cell proliferation in endometrioid endometrial adenocarcinomas.

Endometrioid endometrial carcinomas (EECs) are the most common malignancies of the uterus. Hormonal dependence of EEC, in relation to biomolecular mechanisms involved in tumor progression, such as angiogenesis and cell proliferation, are aspects that can contribute to improving the prognosis of patients. We analyzed the immunoexpression of markers addressed to steroid hormone receptors [estrogen receptor (ER), progesterone receptor (PR)], angiogenesis [cluster of differentiation (CD)105∕endoglin] and cell proliferation (Ki-67) in 50 EECs related to the histopathological prognostic criteria of the lesions. In this study, the ER and PR scores were higher in low grade and early stages EEC, the statistical aspects being variable. The CD105 microvessel density and the Ki-67 proliferation index were superior in high grade and advanced stages EEC, the statistical aspects being significant or at the limit of significance. The ER∕PR and CD105∕Ki-67 immunomarker groups indicated a positive linear intragroup relation and a negative linear intergroup relation, suggesting the presence of synergistic and antagonistic molecular mechanisms of tumor endometrial control that can be used to stratify patients for targeted therapy.

Pediatric Functional Abdominal Pain Disorders following COVID-19.

BACKGROUND: Functional abdominal pain disorders (FAPD) are a group of functional gastrointestinal disorders with multifactorial etiology and are subclassified using Rome IV criteria into a series of clinically distinct entities represented by irritable bowel syndrome, functional dyspepsia, abdominal migraine and functional abdominal pain that is not otherwise specified. Digestive functional disorders associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may be mediated by the involvement of complex pathogenic mechanisms, which have been under investigation in children since the beginning of the coronavirus disease pandemic (COVID-19). METHODS: In this retrospective, observational descriptive and analytical study, we investigated the presence of chronical functional abdominal pain in preschool children (4-6 years old) from the south-west of Romania in the pre-pandemic (18 cases) and COVID-19 pandemic period (34 cases), as well as the association with the COVID-19 positive and COVID-19 negative statuses, gender, environment origin, and viral infection-associated symptoms. Age-specific Rome IV criteria were used to diagnose functional abdominal pain. We performed an integrated statistical analysis of the results utilizing an electronic database in which we compared the data in order to assess the impact of COVID-19 on the clinical-epidemiological parameters analyzed. RESULTS: In the pre-pandemic group, irritable bowel syndrome predominated (77.8%), followed by functional dyspepsia (22.2%), the other types of functional abdominal pain being absent, while for the pandemic group, irritable bowel syndrome was the most common (79.4%), followed by abdominal migraine (11.8%), abdominal dyspepsia (5.9%) and functional abdominal pain not otherwise specified (2.9%). We found a female/male ratio difference of 0.84 and an urban/rural ratio of 1.83 in favor of the pandemic group. These discrepancies were mainly caused by the differences between the COVID-19 positive and negative pandemic groups, where we observed statistical association of the positive pandemic group with IBS and urban environment, and a tendency of FAPDs diagnostic mainly with males. The predominant symptoms associated with COVID-19 positive cases were digestive (60.9%) or respiratory (39.1%). CONCLUSIONS: Our study demonstrates viral-mediated sensitivity of the gastrointestinal tract in preschool children, considering different clinical-epidemiological profiles related to the prevalence of FAPD and according to gender and environment origin, while the contribution of the pandemic context remains to be demonstrated in larger studies.

Immunoexpression of E-cadherin, CD44 and Claudin 7 in gastric adenocarcinomas.

Gastric adenocarcinomas represent frequent malignant tumors in the digestive tract, with a high and constant mortality rate in last decades. The disturbance of the adhesion molecules expression, which normally is essential in maintaining epithelial homeostasis, has a critical role in the initiation and progression of tumors. In this study, we analyzed the immunoexpression of E-cadherin, cluster of differentiation 44 (CD44), and Claudin 7 in 58 cases of gastric adenocarcinomas, in relation to the histopathological parameters of the lesions' aggressiveness. Increased E-cadherin immunoexpression was observed in tubular adenocarcinomas, those of low grade and in stages I-III. CD44 presented high scores in discohesive, hepatoid, tubular, and tubulopapillary adenocarcinomas, those of high grade and in advanced stages. Claudin 7 associated increased scores for tubular, tubulopapillary and micropapillary tumors, those of low grade and mainly in stage I. The markers used in the study can be useful for assessing the aggressiveness of gastric adenocarcinomas, in the context of specific adapted therapy.

Classification and Grading Systems in Gastric Adenocarcinomas.

Gastric adenocarcinomas are lesions that raise important issues in clinical practice, due to their incidence and biological behavior. Over time, various systems have been used for classifying and grading of gastric adenocarcinomas, in the hope of increasing the diagnostic accuracy. In this study we statistically analyzed 112 cases of gastric adenocarcinomas in relation to different classification and grading systems, in order to identify their efficacy and concordance in the histopathological diagnosis. The results indicated a significant association of the Lauren and World Health Organization 2019 classifications and also between these and the three-tier and two-tier grading systems, which supports their practical utility in establishing the diagnosis and assessment of the tumor aggressiveness, for the differentiated therapy.

Immunoexpression of Claudin 4 in Gastric Adenocarcinomas.

Disturbance of the intercellular adhesion system represents a basic biomolecular mechanism in gastric carcinogenesis. Claudin 4 is member of a protein family involved in maintaining homeostasis and epithelial integrity. In this study, we analyzed the immunoexpression of Claudin 4 in 58 cases of gastric adenocarcinomas, in relation to the main histopathological parameters of aggressiveness, the reactions obtained being evaluated through the intensity of the reactions and the number of positive cells. Positive membranous reactions of Claudin 4 were observed in all cases, in tumor cells and some stromal elements, but in some high grade gastric adenocarcinomas also cytoplasmic immunostaining was present. Claudin 4 high scores were associated with tubular, tubulopapillary and hepatoid adenocarcinomas, of low grade and in early stages, aspects that suggest the usefulness of the marker in evaluating the aggressiveness of gastric epithelial tumors.

Immunoexpression of Ki67, p53 and cyclin D1 in osteosarcomas.

The main malignant tumor of the bone tissue is represented by osteosarcoma, neoplasia with a reserved prognosis and an unpredictable evolution, often aggressive. Cell cycle disruption is one of the complex biomolecular mechanisms involved in the progression of osteosarcomas. In this study, we analyzed the immunoexpression of Ki67, p53 and cyclin D1 for 18 primitive osteosarcomas in relation to the clinicopathological prognosis parameters of the lesions. The results indicated the predominance of lesions in male young patients, with femoral location, most tumors being represented by the osteoblastic type, with high grade, size <8 cm and in advanced stages. Reactions were present in all cases, the high immunoexpression being associated with osteoblastic∕epithelioid types (Ki67, cyclin D1, p53), high grade (Ki67, cyclin D1) and advanced stage (Ki67, cyclin D1). The study revealed a positive linear relation of the investigated immunomarkers expression, which indicates their usefulness in identifying lesions with aggressive progression potential.

Analysis of Biochemical Parameters in Children with Chronic Tonsillitis.

Chronic tonsillitis are frequent in pediatric pathology with numerous involved risk factors and pathogenic mechanisms. In this study, epidemiological data and biochemical values addressed to inflammation and mineral, lipid and hepatic metabolism were analyzed for 37 children of school age with chronic tonsillitis. We found that in the majority of cases, chronic tonsillitis was associated with increasing number of blood circulating inflammatory cells, high values of transaminases, cholesterol, triglycerides and low values of procalcitonin, C-reactive protein, calcium, vitamin D and serum iron. The results indicated relations of the biochemical profile analyzed with risk factors and systemic mechanisms for initiation and maintenance of chronic tonsillitis, aspects that can be used to optimize the prognosis of chronic tonsillitis in children.

Comparative clinicopathological aspects of chronic tonsillitis and adenoiditis in children.

Chronic palatal and nasopharyngeal inflammations are common lesions in pediatric pathology, with major effects on children's development. The study included 34 cases of chronic tonsillitis and adenoiditis for which we quantified immunohistochemically and analyzed the distribution of inflammatory elements in the follicular, extrafollicular and epithelial compartments, in relation to the composite histological scores and the clinico-epidemiological profile of the lesions. The cases were more frequent under the age of 10, in female patients, coming from urban areas, with the diagnosis of tonsillitis. B-lymphocytes have been associated with follicular areas in tonsillitis and epithelial areas in adenoiditis. In all compartments, T-lymphocytes were more frequently associated with tonsillitis and plasma cells associated with adenoiditis. Macrophages and dendritic cells had a relatively uniform distribution for the three compartments in all cases. The results obtained indicate different inflammatory phenotypes for chronic tonsillitis and adenoiditis, an aspect that may be useful for stratifying patients for optimal therapy.

Clinico-imaging and morphological aspects of the benign serous ovarian epithelial tumors in children and adolescents.

Benign serous ovarian epithelial tumors represent a major area of interest in pediatric pathology through the incidence and the hormonal and reproductive implications that they induce. In this study, we analyzed 24 tumors diagnosed and surgically operated in children and adolescents, in relation to clinical, histological and immunohistochemical parameters, which can provide information on the potential for growth of lesions. The average age of diagnosis was 13.2 years, the majority of tumors being present in patients over 10 years (75%), with accompanying symptoms (83.3%), unilateral (91.7%) and dimensions of maximum 10 cm (66.7%). The histopathological aspect indicated a cystic growth pattern, sometimes papillary, and in three cases, the presence of atypical focal areas of the tumor epithelium. The Ki67 proliferation index values were higher in the case of tumors larger than 10 cm, those with papillary pattern, and in those with atypical areas, while p53 reactions were present only in cases with atypical proliferation areas. The parameters investigated in this study are useful both for assessing the risk of tumor growth and progression, as well as for stratifying patients for active clinical surveillance.

Clinico-pathological study of chronic rhinitis in adolescents.

Through the increasing incidence and association of asthma, chronic rhinitis (CR) raises major problems in the pathology of children and adolescents. The evaluation of the inflammatory status together with the diagnosis and the tandem treatment of the two conditions can contribute to the improvement of the patients' quality of life. In this study, we analyzed the immunoexpression of cluster of differentiation (CD) 20, CD8, CD138 and eosinophil major basic protein (MBP) in 24 cases of CR in adolescents, in eight of them existing the association of asthma. Symptoms of CR and allergic status, as well as histopathological changes specific to a persistent inflammation, were identified in this study. The CD20∕CD8 immunophenotype was more specific for CR, while the CD138∕eosinophil MBP immunophenotype was specific for asthma-associated chronic rhinitis (AACR). The negative linear distribution of lymphocyte elements compared to plasmocytes and eosinophils specific for the allergic status can support the protective effect of CD8 T-lymphocytes and the presence of a semi-activated B-lymphocyte status in CR. The results may be useful for improving the stratification criteria of patients for therapy.

The involvement of EGFR, HER2 and HER3 in the basal cell carcinomas aggressiveness.

Basal cell carcinomas (BCCs) are the most common malignant skin tumors, with variable prognosis and recurrence rates, depending on histopathological subtypes. The study analyzed the immunoexpression of epidermal growth factor receptors (EGFRs) in 53 cases of nodular, adenoid and morpheaform BCCs in relation to clinico-pathological associated parameters. We found significant differences in the expression of EGFR, HER2 and HER3 reported to histological BCC types. The nodular type presented the weakest expression of EGFRs, while the morpheaform type had a high expression of all receptors and the adenoid type an increased expression only in case of EGFR and HER2. This study supports the involvement of EGFR, HER2 and HER3 in BCC aggressiveness of and in tumor differentiating towards different histological subtypes.

Clear cell renal cell carcinomas - epithelial and mesenchymal immunophenotype.

Clear cell renal cell carcinomas (CCRCCs) are the most common kidney tumors that despite current advances in diagnosis continue to have high rates of metastasis and mortality. In this study, we analyzed the cytokeratin (CK) AE1∕AE3 and vimentin immunoexpression in 26 CCRCCs in relation to histopathological prognostic parameters. Immunoreactions were positive and heterogeneous in all analyzed cases. CK AE1∕AE3 immunoexpression was associated with low grade and early stage lesions, while vimentin immunoexpression was associated with high grade and advanced lesions. The aspect may be used to determine the tumor heterogeneity and a better patients' stratification for therapy.

A rare case of a Wilms tumor: case report.

The nephroblastoma or Wilms tumor (WT) is the most common renal tumor in childhood, representing approximately 6-7% of all pediatric cancers, with a yearly incidence of 10 cases in one million children less than 15 years old, and continues to arouse interest by remarkable actual therapeutic successes, consecutive to the multidisciplinary approach. Its maximum incidence is around the age of 3-3.5 years old, having an equal frequency in males and females. We present the case of a child, aged three years and five months, who was diagnosed with WT (nephroblastoma) with triphasic pattern, stage II tumor, and admitted to the Department of Oncopediatry for chemotherapeutic treatment and clinico-biological investigations.

Immunoexpression of transcription factors in urothelial bladder carcinomas.

Transcription factors play a central role in the epithelial-mesenchymal transition (EMT), which is one of the biomolecular mechanisms involved in the progression of urothelial carcinomas of the bladder (UCB). In this study, we analyzed the immunoexpression of Twist 1, Snail, Slug and ß-catenin in relation to histopathological prognostic parameters of UCB. The obtained results indicated the association of Snail and ß-catenin expression with low grade and early stage of UCB, as well as the association of Twist 1 and Slug expression with high grade and advanced stage lesions. The specific or sequential action of transcription factors in the bladder tumoral EMT may be useful for identifying the aggressive lesions.