Considering Histologic Remission in Ulcerative Colitis as a Long-Term Target.

Monitoring disease activity in inflammatory bowel disease (IBD) is challenging since clinical manifestations do not represent reliable surrogates for an accurate reflection of the inflammatory burden. Endoscopic remission had been the most significant endpoint target in the last years; nevertheless, a remarkable proportion of patients continue to relapse despite a normal-appearing mucosa, highlighting that endoscopy may underestimate the true extent of the disease. A subtle hint of the importance that histology plays in the long-term course of the disease has been endorsed by the STRIDE-II consensus, which recommends considering histologic healing for ulcerative colitis (UC), even though it is not stated to be a compulsory formal target. It is a continuum-changing paradigm, and it is almost a certainty that in the near future, histologic healing may become the new formal target for ulcerative colitis. It must be emphasized that there is great heterogeneity in defining histological remission, and the main criteria or cut-off values for inflammatory markers are still in an ill-defined area. The complexity of some histologic scores is a source of confusion among clinicians and pathologists, leading to low adherence in clinical practice when it comes to a homogenous histopathological report. Therefore, a standardized and more practical approach is urgently needed.

Statical Association between Clinical and Histopathological Parameters for Keratinocyte Carcinomas.

The most common tumor of the western world is comprised of forms of non-melanoma skin cancers, previously known as keratinocyte carcinomas (KCs) The purpose of this study was to determine de incidence of non-melanoma skin tumors and the relationship between histopathological risk factors in patients with skin cancers. The study was composed from 332 cases of skin malignancies for which clinical and histopathological aggressivity factors were statistically analyzed through comparison tests and also stored digitally. For basal cell carcinoma (BCC) statistical analysis indicated significant relationships between pT category and gender, tumor size, ulceration, depth of invasion and positive resection limits. For squamous cell carcinoma (SCC) statistical analysis indicated significant relationships between pT category and tumor size, depth of invasion and positive resection limits. Clinical and histological analysis of certain characteristics of the above-mentioned skin cancers is an essential step in documenting and improving both prognosis and therapy standards.

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.

VEGF Immunoexpression in Endometrioid Endometrial Carcinomas.

Vascular endothelial growth factor (VEGF) is the most important stimulator of endometrial tumor angiogenesis, a mechanism that may be a therapeutic target in the context of an incidence and persistent mortality of endometrial endometrial carcinomas (EEC). In this study, VEGF immunoexpression was analyzed for 50 cases of EEC in relation to the histopathological parameters of tumor aggressiveness. High VEGF scores have been associated with the high grade and advanced stage of EEC, but unrelated to the depth of myometrial invasion, the pattern of tumor invasion, or vascular invasion. VEGF may be useful for assessing EEC aggression, but also for tumor angiogenic potential, which recommends it as a possible mark for specific antitumor therapy.

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.

The role of cell adhesion molecules in the progression of bladder urothelial carcinomas.

Alteration of the intercellular adhesion system plays an essential role in the initiation and progression of bladder carcinomas. We followed the immunoexpression of adhesion molecules, E-cadherin, ß-catenin and Claudin-1, in relation to the histopathological grade and the pT category in a number of 50 urothelial carcinomas of the bladder, based on a final staining score (FSS), calculated on the basis of reaction intensity and labeled cells number. E-cadherin immunoexpression was identified in the membrane of tumor cells, low FSS being associated with invasive high-grade carcinomas. ß-catenin reactions were membranous in the case of low-grade noninvasive carcinomas and predominantly cytoplasmic and nuclear in the case of high-grade invasive ones, for which high FSS were associated. Claudin-1 was identified at the membrane level, the high FSS values being more frequent in the case of high-grade invasive carcinomas, although there were no significant statistical associations. Loss of E-cadherin expression and the associated positive linear relation of ß-catenin and Claudin-1 indicate the usefulness of the analyzed markers in identifying the invasive aggressive phenotype of urothelial bladder carcinomas.

Non-Melanoma Skin Cancer: Statistical Associations between Clinical Parameters.

Non-melanoma skin cancer (NMSC) represent an important health problem in medical practice. This is the most frequent type of cancer and its incidence is constantly increasing. Basal cell carcinoma and squamous cell carcinoma constitute the majority of NMSC, respectively 70% and 25% of total cases. The present retrospective study was conducted over a one-year period and included 439 cases of NMSC, of which 336 BCC and 103 SCC. We analyzed a series of clinical parameters: gender, age, tumor size and tumor topography. The statistical analysis of the investigated parameters indicated gender-age associations for BCC, and topography-gender, as well as topography-age for SCC.

Histopathological Study of the Prostate Cancer Growth Patterns in Relation with the Grading Systems.

Prostate adenocarcinomas are common lesions with a high incidence and variable prognosis, which can be assessed using tumor grading systems. In this study, we analyzed 329 prostate adenocarcinomas in relation to tumor variants, growth patterns, classical and updated grading systems. The study indicated statistical associations of atrophic, pseudohyperplastic and microcystic variants with low grading scores, the associations of glomeruloid, cribriform with or without necrosis and signet ring-like cell variants with high grading scores, and also of single growth patterns with intermediate scores, which supports the accordance and usefulness of existing grading systems for the identification of aggressive prostate tumor lesions.

Ezrin Immunoexpression in Prostate Adenocarcinomas.

Ezrin is a component of cell surface structures, the most important member of the Ezrin/radixin/moesin family. In this study, we aimed to evaluate the expression of ezrin in 50 cases of prostate carcinoma (PA) in relation to the ISUP (International Society of Urological Pathology) groups. Ezrin expression analysis was identified in 78% of the PA cases investigated, with predominantly cytoplasmic staining pattern and variable intensity. Overall, we observed an increase in the intensity of the immunostaining progressively with the decrease in cell differentiation. Statistical analysis indicated the predominance of high FSS in the ISUP 4-5 groups and low FSS in the ISUP 1-2 groups, aspects that were statistically significant. Ezrin was expressed in the majority of PAs analyzed and its expression was associated with ISUP grades, an aspect that suggests involvement in PA progression.

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.

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 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.

VEGF Immunoexpression in Prostate Adenocarcinoma.

Angiogenesis is a basic biomolecular mechanism for tumor progression, the vascular endothelial growth factor (VEGF) being one of the main enhancers of this complex process. In this study, we analyzed VEGF-A immunoexpression in 61 prostate adenocarcinomas (PAs), related to the prognostic parameters of the lesions. VEGF scores were higher in PAs that associated serum PSA values above 20ng/ml, in tumors with pure complex or mixed growth patterns, as well as in high-grade and advanced lesions. The results obtained indicate the involvement of VEGF in prostate angiogenesis and the usefulness of the maker for the identification of aggressive lesions.

Clinicopathological Correlations in Cutaneous Squamous Cell Carcinomas.

Squamous cell carcinomas (SCC) represent 20% of all nonmelanoma skin cancers, most tumors responding favorably to the conventional therapy. Incisional or excisional biopsy is essential for diagnosis and prognosis evaluation. The study included 103 cases of SCC, following the assessment of some clinical and histopathological aggressivity factors, which were digitally stored and statistically analyzed using comparison tests. The tumor grade was significantly associated with the histological variant, the maximum tumor size, the perineural and lymphovascular invasion, the depth of the invasion and the status of resection limits. The pT category was significantly associated with the location and maximum tumor size, perineural invasion, depth of invasion and status of resection limits. It was observed a significant association of tumor grade and pT category. The evaluation of the clinical and histological characteristics of SCC is an important step in obtaining relevant prognostic information and applying appropriate therapy.

E-cadherin, fibronectin and Slug immunoexpression in non-melanoma skin cancers.

Epithelial-mesenchymal transition (EMT) is an essential biological process involved in the initiation and progression of cancer by which epithelial tumor cells lose their differentiated characteristics, such as cell-cell adhesion and apical-basal polarity and acquire a more invasive and∕or metastatic mesenchymal phenotype. The present study investigated the expression of immunomarkers with a role in EMT of non-melanoma skin cancers (NMSCs), such as E-cadherin, fibronectin and Slug, for a number of 50 NMSCs, represented by 30 cases of basal cell carcinomas (BCCs) and 20 cases of squamous cell carcinomas (SCCs). For BCC, the statistical analysis of the investigated immunomarkers indicated significantly differences in relation to the depth of invasion, and for E-cadherin and fibronectin with the degree of risk. In the case of SCC, the statistical analysis indicated significant differences of E-cadherin and Slug with the degree of tumor differentiation, and for fibronectin and Slug with the depth of invasion. The analysis of the distribution for the percentage values of the investigated immunomarkers in the case of BCC indicated a significant negative linear relation between E-cadherin/fibronectin and E-cadherin/Slug, and in SCC a significant negative linear relation between E-cadherin∕fibronectin, E-cadherin∕Slug and a positive linear one in the case of fibronectin∕Slug. The study indicates through the statistically significant relation between E-cadherin∕fibronectin and E-cadherin∕Slug, the EMT intervention in carcinogenesis of NMSC.

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.

Presepsin as a Potential Prognostic Marker for Sepsis According to Actual Practice Guidelines.

The 2016 Surviving Sepsis Campaign guidelines define sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection. This study had the objective of assessing the efficacy of presepsin in the prognosis of sepsis. This was a single-center prospective study, performed in Craiova Emergency Hospital, that included 114 patients admitted in the Intensive Care Unit (ICU) department between 2018 and 2019 fulfilling the sepsis criteria. Including criteria were: age ≥ 18, sepsis diagnosed by the Sequential Organ Failure Assessment (SOFA) score of pulmonary, abdominal, urinary, surgical or unknown origin, as well as lactate levels ≥ 2 mmol/l and need of vasopressors for mean arterial pressure (MAP) ≥ 65 mmHg, despite adequate volume resuscitations for patients with septic shock. Patients younger than 18, pregnant, immunocompromised, or with terminal illnesses were excluded. Based on disease severity, patients were distributed into two study groups: sepsis-76 patients and septic shock-38 patients. As expected, SOFA score and most of its components (PaO2/FiO2, platelets, and Glasgow Coma Score (GCS)) were significantly modified for patients with septic shock compared to those in the sepsis group and for survivors versus non-survivors. Overall death rate was 34.2%, with a significantly higher value for patients with septic shock (55.3% vs. 23.7%, p = 0.035). Sepsis marker presepsin was significantly elevated in all patients (2047 ng/mL) and significantly increased for the septic shock patients (2538 ng/mL, p < 0.001) and non-survivors (3138 ng/mL, p < 0.001). A significant correlation was identified between the SOFA score and presepsin (r = 0.883, p < 0.001). The receiver operating characteristics (ROC)-Area Under Curve (AUC) analysis showed significant prognostic values for presepsin regarding both sepsis severity (AUC = 0.726, 95% confidence interval CI = 0.635-0.806) and mortality risk (AUC = 0.861, 95%CI = 0.784-0.919). In conclusion, under the revised definition of sepsis, presepsin could be a useful marker for prognosis of sepsis severity and mortality risk. Additional data are required to confirm the value of presepsin in sepsis prognosis.

Histopathological Features of the Eyelid Basal Cell Carcinomas.

Basal cell carcinomas (BCC) make up about 90% of malignant tumors of the eyelids. Although they are generally slow-growing tumors, in the periocular region can cause significant morbidity due to orbital invasion. In the present study we followed the associations between the various types of BCC with the depth of invasion, respectively the Breslow stage (BS) and with the pT category. The study included a number of 92 cases of eyelid BCC from the Plastic Surgery and Ophthalmology Departments of the Craiova County Emergency Clinical Hospital which were processed and diagnosed in the Pathological Laboratory of the same hospital. Histopathological analysis of the 92 BCCs indicated that in 72 cases the tumors were composed of a single growth pattern, and in 20 cases they were composite, associating two or more growth patterns. The cases with a single growth pattern corresponded in 53 cases of nodular BCC, in 9 cases of infiltrative BCC, in 2 cases of superficial BCC and in 8 cases of micronodular BCC. The composite types corresponded in 10 cases to the association of the nodular type with the micronodular one, in 8 cases to the association of the nodular type with the infiltrative one and in 2 cases to the association of the infiltrative type with the micronodular one. Statistical analysis indicated significant associations between BS, pTa and the histopathological type of tumors, the mixed types being frequently present in cases with high SB and advanced pT.

Histopathological Features of Chronic Rhinosinusitis with Nasal Allergic Polyps.

Chronic rhinosinusitis with nasal polyps of allergic etiology is one of the most common pathology in the ENT sphere that affect a significant percentage of population. The paper aims to establish the involvement of the allergic component in the genesis of nasal polyposis. The study included 150 nasal polyps from patients hospitalized and operated in the ENT Department of Craiova's Clinical Emergency County Hospital. The biological material was fixed in 10% buffered formalin, processed by classical paraffin embedding technique followed by hematoxylin-eosin staining and it was interpreted in the Pathology Department of the same hospital. We evaluated a number of histopathological parameters that were given severity scores. The most common changes at epithelial level were: basal layer hyperplasia observed in 87 cases (58%), goblet cell hyperplasia in 121 cases (80.66%), basal membrane thickening with values between 10-42µm corresponding to a number of 118 cases (78.66%). The most important stromal changes were edema in 88% and infiltration with eosinophils 100%, indicating the allergic nature of this disease.