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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.
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Adenocarcinoma , Biomarcadores Tumorais , Peptídeo Relacionado com Gene de Calcitonina , Proteína Semelhante a Receptor de Calcitonina , Neoplasias Colorretais , Humanos , Masculino , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/sangue , Feminino , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/sangue , Pessoa de Meia-Idade , Idoso , Proteína Semelhante a Receptor de Calcitonina/metabolismo , Proteína Semelhante a Receptor de Calcitonina/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Estadiamento de Neoplasias , Adulto , Idoso de 80 Anos ou mais , Prognóstico , Regulação Neoplásica da Expressão GênicaRESUMO
We conducted a retrospective, observational study, based on 91 patients diagnosed with colorectal cancer (CRC), hospitalized and evaluated within the Surgical and the 2nd Internal Medicine Clinic, the Clinical Emergency County Hospital Craiova, between October 2020 and October 2022. We aimed in this study to analyze the epidemiological aspects and clinical characteristics of patients with CRC. In our study group, the patients' ages were between 30-89 years, with mean a of 68.06 (±9.39) years. The incidence of CRC cases in young patients was relatively low. 56.04% of all patients lived in urban areas. In 57.14% of cases, tumors were found on the left colon. The histopathological (HP) examination revealed the net predominance of adenocarcinoma. Depending on the HP grade, the tumor formations were represented predominantly by moderate and poorly differentiated tumors, having G2 and G3 grades. The T3 tumors predominated the total tumors identified. We observed that obstructions have the highest percentages on the left colon, while haemorrhages and perforations have higher percentages on the right side of the colon. The results obtained in our study largely validated the hypothesis proposed at the beginning of the study, according to which, using the clinical, paraclinical, and HP data, we can create a typology of the patient with CRC, from the Craiova Reference Center, to guide us in identifying some measures to decrease the percentage of CRC, as well as to improve the efficiency of the surgical treatment for these cases.
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Background: Urosepsis is a life-threatening medical condition due to a systemic infection that originates in the urinary tract. Early diagnosis and treatment of urosepsis are critical to reducing mortality rates and preventing complications. Our study was aimed at identifying a fast and reliable method for early urosepsis diagnosis and severity assessment by combining prognostic scores such as SOFA and NEWS with ultrasound examination and serum markers PCT and NLR. Methods: We performed a single-center prospective observational study in the Craiova Clinical Emergency Hospital. It initially analysed 204 patients admitted for sepsis of various origins in our hospital between June and October 2023. Those with urological conditions that were suspected to have urosepsis have been selected for the study so that finally 76 patients were included as follows: the severe cases with persistent hypotension requiring vasopressor were enrolled in the septic shock group (15 patients - 19.7%), while the rest were included in the sepsis group (61 patients - 80.3%). Mortality rate in our study was 10.5% (8/76 deaths due to sepsis). Results: Both prognostic scores SOFA and NEWS were significantly elevated in the septic shock group, as were the sepsis markers PCT and NLR. We identified a strong significant positive correlation between the NEWS and SOFA scores (r = 0.793) as well as PCT and NLR (r=0.417). Ultrasound emergency evaluation proved to be similar to CT scan in the diagnosis of urosepsis (RR = 0.944, p=0.264). ROC analysis showed similar diagnostic performance for both scores (AUC = 0.874 for SOFA and 0.791 for NEWS), PCT and NLR (AUC = 0.743 and 0.717). Conclusion: Our results indicate that an accurate and fast diagnosis of urosepsis and its severity may be accomplished by combining the use of simpler tools like emergency ultrasound, the NEWS score and NLR which provide a similar diagnosis performance as other more complex evaluations.
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Cancer remains a significant global cause of mortality, irrespective of a country's level of development. Among all cancer types, gastrointestinal cancers claim the highest number of lives annually. This disease predominantly affects individuals in their 6th to 8th decades of life. Unfortunately, diagnoses often occur during advanced stages of the illness, rendering chemotherapy less effective and offering a reserved prognosis. Conventional endoscopy, however, struggles to differentiate lesions based on their histological composition. Consequently, the management of patients largely depends on histopathological examinations, which can be time-consuming. Biopsy results are sometimes delayed, with precious weeks passing, particularly critical for patients with malignant lesions. Moreover, biopsies may yield inconclusive results if not precisely targeted, leading to potential mismanagement, unnecessary resections and burdensome pathology services. This series of cases underscores, as previous studies have, the value of modern endoscopic techniques in determining the appropriate therapeutic approach for each patient, an approach that ensures the highest quality of life.
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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.
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Adenocarcinoma , Neoplasias da Próstata , Masculino , Humanos , Claudina-3 , Próstata/metabolismo , Próstata/patologia , Claudinas/metabolismo , Claudina-4 , Neoplasias da Próstata/patologia , Adenocarcinoma/patologiaRESUMO
One of the molecular routes of colorectal carcinogenesis is the lack of mismatch repair (MMR) proteins, which may have substantial clinical consequences in predicting therapy success. This study aimed to analyze the expression of the MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), and MutS homolog 6 (MSH6) in a cohort of 91 colorectal cancer (CRC) patients, and to evaluate the relationship between patient clinicopathological characteristics and immunoexpression of these biomarkers. In this study, we obtained the highest scores of the MLH1 immunoexpression in non-mucinous tumors, moderately differentiated lesions, and in stage IV. The highest values of the MSH2 and MSH6 scores were observed in mucinous tumors, and poorly differentiated lesions, in stages II-III, and stages III-IV, respectively. To improve the stratification criteria for targeted oncological therapy and to predict patient outcomes, markers used may help evaluate the aggressiveness of lesions.
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Acute pancreatitis is characterized as an inflammatory illness that is life-threatening and causes necrosis as well as simple edema when pancreatic enzymes are activated intraglandularly. It is not known whether severe acute respiratory syndrome coronavirus 2 causes acute pancreatitis. Patients with acute pancreatitis who test positive for coronavirus disease 2019 (COVID-19) frequently have biliary or alcoholic causes. It is unclear how common acute pancreatitis is in patients with COVID-19. By contrast with patients without COVID-19, however, COVID-19-positive patients with acute pancreatitis have a higher mortality as well as a higher risk of necrosis and admission to an intensive care unit. The most common cause of mortality in COVID-19-positive individuals with concurrent severe pancreatitis is acute respiratory distress syndrome. The present study discussed research on the link between COVID-19 infection and acute pancreatitis.
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Polymyalgia rheumatica (PMR) is a chronic inflammatory disease which affects the connective vascular tissue, characterized by pain accompanied by morning stiffness, predominantly of the neck muscles, hip and shoulder girdle. Usually, patients with this disease are >50 years of age and biological inflammatory syndrome is present with an increase in both the erythrocyte sedimentation rate and C-reactive protein levels, aspects similar to giant cell arteritis. The aim of the present review was to depict the current pathogenic hypothesis, diagnostic and treatment approach for patients with PMR, and novelties since the development of the currently used 2012 European League Against Rheumatism and American College of Rheumatology provisional classification criteria. PMR is a prevalent disease that can occasionally prove difficult to diagnose and treat. Possibly, the most abundant type of evidence and data revealed over the past decade have been acquired through musculoskeletal imaging, with implications in diagnosis, disease monitoring and relapse, prognosis and changes with treatment. Further research on pathophysiology is required to gain a deeper understanding of the underlying processes, which will serve as the foundation for future personalized treatments. In addition, there is an increasing demand for improved diagnostic techniques, which should include a further development of various imaging modalities, in order to provide accurate diagnosis and appropriate therapy.
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The aim of the present study was to determine the health-related quality of life of stroke patients and their caregivers during the fifth wave of the COVID-19 pandemic. A total of 70 patients who had been diagnosed with stroke between October 2021 and March 2022 and 70 caregivers were included in the present study. A prospective follow-up study assessing the quality of life at baseline was conducted after 3 months for both patients and their caregivers. A linear regression analysis was performed to evaluate potential associations between quality of life and assessed factors. The results revealed that age, sex, employment status, hospitalization period, type of stroke, Barthel index for activities of daily living (ADL) and discharge Modified Rankin Scale (mRS), were significant determinants of the 90-day Health-Related Quality of Life (HRQoL). An important clinical change in the QoL score was estimated for both post-stroke patients and their caregivers. The decrease of the HRQoL of patients was statistically influenced by a higher value of ADL (P=0.014), whereas, in the case of their caregivers, the decrease of HRQoL was primarily influenced by the QoL of patients after 3 months (P=0.043). The present study identified some important key factors with direct consequences on HRQoL regarding stroke survivors and their caregivers.
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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.
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(1) Background: The assessment of mortality and rebleeding rate in upper gastrointestinal bleeding (UGIB) is essential, and several prognostic scores have been proposed. Some patients with UGIB did not undergo endoscopy, either because they refused the procedure, suffered from alcohol withdrawal symptoms or altered general status, or because the bleeding was severe enough to cause death before the endoscopy. The mortality risk in the subgroup of patients without endoscopy is poorly evaluated in the literature. (2) Methods: The purpose of the study was to identify the most useful scores for the assessment of in-hospital mortality in patients with UGIB with no endoscopy performed and no known etiology. A total of 198 patients with UGIB and no endoscopy performed were admitted between January 2017 and December 2021 and the accuracy of 12 prognostic scores and the Charlson comorbidity index for in-hospital mortality prediction were analyzed, as well as Child-Pugh Turcotte (CPT) and Meld scores in patients with cirrhosis. (3) Results: The mortality rate was 37.9%, higher than in variceal (21.9%, p < 0.0001) and non-variceal bleeding (7.4%, p < 0.0001). The most accurate scores by AUC were the International Bleeding score (INBS, 0.844), Glasgow Blatchford (0.783), MAP score (0.78), Iino (0.766), AIM65 and modified N-score (0.745 each), modified Glasgow-Blatchford (0.73), H3B2 and N-score (0.701); Rockall, Baylor, and T-score had an AUC below 0.7. MELD score was superior to CPT in patients with cirrhosis (AUC 0.811 versus 0.670). (4) Conclusions: The mortality rate in UGIB with no endoscopy was higher than in both variceal and non-variceal bleeding and was higher in the pandemic period but with no statistical significance (45.3% versus 32.14%, p = 0.0586), mainly because of positive cases. Only one case of rebleeding was noted; the hospitalization period was significantly shorter. The most accurate score was International Bleeding Score; the MELD score had a higher but moderate accuracy compared with CPT in patients with cirrhosis.
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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.
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Endometrial carcinoma is one of the most prevalent cancers affecting women with epidemiological placing it as the sixth most common cancer in women. One of the factors implicated in EMT (epithelial-mesenchymal transition), Snail is regarded as having a pivotal role. We selected a number of 30 endometrial carcinomas, in a 2-year period (2020-2022). Snail immunoexpression was identified in the tumor cells for 70% of the endometroid carcinoma cases studied. Tumor cells showed both nuclear and cytoplasmic expression but only nuclear signals were quantified. The average percent of marked tumor cells was 38.6±24.9, corresponding to well differentiated carcinomas. Our analysis also showed a significant association between higher tumor grade and snail expression (p=0.000). Alteration of the epithelial-mesenchymal phenotype in endometrial carcinomas by Snail overexpression in high-grade and advanced-stage lesions constitutes mechanisms involved in the process of tumor progression.
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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.
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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.
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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.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Caderinas , Adenocarcinoma/patologia , Neoplasias Gástricas/patologia , Claudinas , Biomarcadores Tumorais , Receptores de HialuronatosRESUMO
Rheumatoid arthritis (RA) is considered a systemic inflammatory disease marked by polyarthritis which affects the joints symmetrically, leading to progressive damage of the bone structure and eventually joint deformity. Lung involvement is the most prevalent extra-articular feature of RA, affecting 10-60% of patients with this disease. In this review, we aim to discuss the patterns of RA interstitial lung disease (ILD), the molecular mechanisms involved in the pathogenesis of ILD in RA, and also the therapeutic challenges in this particular extra-articular manifestation. The pathophysiology of RA-ILD has been linked to biomarkers such as anti-citrullinated protein antibodies (ACPAs), MUC5B mutation, Krebs von den Lungen 6 (KL-6), and other environmental factors such as smoking. Patients at the highest risk for RA-ILD and those most likely to advance will be identified using biomarkers. The hope is that finding biomarkers with good performance characteristics would help researchers better understand the pathophysiology of RA-ILD and, in turn, lead to the development of tailored therapeutics for this severe RA manifestation.
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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.
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Antígenos CD , Caderinas , Fibronectinas , Neoplasias Cutâneas , Fatores de Transcrição da Família Snail , Antígenos CD/biossíntese , Antígenos CD/imunologia , Caderinas/biossíntese , Caderinas/imunologia , Transição Epitelial-Mesenquimal , Fibronectinas/biossíntese , Fibronectinas/imunologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Fatores de Transcrição da Família Snail/biossíntese , Fatores de Transcrição da Família Snail/imunologiaRESUMO
INTRODUCTION: Performing a colonoscopy allows the examination of the entire colon and the assessment of polyps. PATIENTS, MATERIALS AND METHODS: We performed a retrospective analysis of prospectively collected data from January 2018 until February 2020 (two years), in which we enrolled a number of 210 patients performing colonoscopy in the Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, Romania. We performed 326 polypectomies. RESULTS: We classified the polyps into diminutive (n=169), small (n=103) and large polyps (n=54). Regarding the polypectomy technique, our results indicated that 40 out of 48 (83.3%) polypectomies with the biopsy forceps were complete, as well as 27 out of 31 (87.1%) cold snare polypectomies and 12 out of 14 (85.7%) hot snare polypectomies. The differences were not statistically significant (p=0.116). Regarding the number of incomplete polypectomies, our data suggests that the high expertise endoscopist had two incomplete resections (5.1% of total), the medium expertise endoscopist 1 had also two incomplete resections (11.1% of total), the medium expertise endoscopist 2 had three incomplete resections (15% of total), the limited expertise endoscopist 1 had three incomplete resections (27.27% of total) and the limited expertise endoscopist 2 had four incomplete resections (30.76% of total). Analyzing the data, the differences were statistically significant (p=0.006). CONCLUSIONS: Our study is able to suggest that high-definition white-light endoscopy (HD-WLE) macroscopic visualization of the polyp resection site is not enough to assess complete polyp resection and follow-up colonoscopy should be performed for cases with incomplete margins of resection.
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Pólipos do Colo , Neoplasias Colorretais , Biópsia , Pólipos do Colo/cirurgia , Colonoscopia , Neoplasias Colorretais/cirurgia , Humanos , Estudos RetrospectivosRESUMO
Alteration of cadherin immunophenotype is associated with the epithelial-mesenchymal transition, a complex biomolecular mechanism involved in carcinomas progression. The study investigated the immunoexpression of E-, P- and N-cadherins in 50 serous malignant tumors of ovary related to the histopathological prognostic parameters of the lesions, using a quantification based on scores that took into account the number of marked cells and the intensity of the reactions. The E-cadherin and P-cadherin immunostainings were significantly superior in serous borderline tumors (SBTs) compared to carcinomas, as well as in advanced carcinomas compared to early stages. Although the immunoreactions indicated higher scores in high-grade serous carcinomas (HGSCs) versus low-grade ones (LGSCs), the aspect was without statistical significance. Immunoreactions of N-cadherin were present only in HGSC, being significantly superior in the advanced stages of tumors. Ovarian serous malignant tumors expressed E-, P- and N-cadherins in different proportions, the altered cadherin phenotype being associated with progression of the disease. The results can be used to identify tumors with progression potential and to better stratify patients for specific therapy.