Determination of VEGFR-2 (KDR) 604A>G Polymorphism in Pancreatic Disorders.

Pancreatic disorders have a high prevalence worldwide. Despite the fact that screening methods became more effective and the knowledge we have nowadays about pancreatic diseases has enhanced, their incidence remains high. Our purpose was to determine whether single nucleotide polymorphism (SNP) of VEGFR-2/KDR (vascular endothelial growth factor receptor 2/kinase insert domain receptor) influences susceptibility to develop pancreatic pathology. Genomic DNA was extracted from blood samples collected from patients diagnosed with acute pancreatitis (n = 110), chronic pancreatitis (n = 25), pancreatic cancer (n = 82) and healthy controls (n = 232). VEGFR-2 (KDR) 604A>G (rs2071559) polymorphism frequency was determined with TaqMan allelic discrimination assays. Statistical assessment was performed by associating genetic polymorphism with clinical and pathological data. In both pancreatic disorders and healthy control groups the polymorphism we studied was in Hardy-Weinberg equilibrium. Association between increased risk for pancreatic disorders and studied polymorphism was statistically significant. KDR 604AG and AG + GG genotypes were more prevalent in acute pancreatitis and pancreatic cancer patients than in controls. These genotypes influence disease development in a low rate. No association was found between chronic pancreatitis and KDR 604AG and AG + GG genotypes. In Romanian cohort, we found an association between the KDR 604A→G polymorphism and acute pancreatitis and pancreatic cancer. Carriers of the -604G variant allele were more frequent among acute pancreatitis and pancreatic cancer than among controls, suggesting that KDR 604G allele may confer an increased risk for these diseases. In the future, more extensive studies on larger groups are necessary, in order to clarify the role of VEGFR2 polymorphisms in pancreatic pathology.

Prothrombotic status in COVID­19 with diabetes mellitus (Review).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused an important social and health impact worldwide and the coronavirus disease-19 (COVID-19) has elicited devastating economy problems. The pathogenesis of SARS-CoV-2 infection is a complex mechanism and is considered to be the result of a challenging interaction, in which host and virus immune responses are the key elements. In this process, several inflammatory pathways are involved, and their initiation can have multiple consequences with a considerable impact on evolution, such as hyperinflammation and cytokine storm, thereby promoting activation of the coagulation system and fibrinolytic activity suppression. It is commonly recognized that COVID-19 severity involves multiple factors, including diabetes which increases the risk of developing different complications. This could be as a result of the low-grade inflammation as well as the innate and adaptive immune response dysfunction that is observed in patients with diabetes mellitus. In patients with diabetes, multiple metabolic disturbances which have a major impact in disturbing the balance between coagulation and fibrinolysis were discovered, thus the risk for thrombotic events is increased. Diabetes has been recognized as an important severity prognosis factor in COVID-19 cases and considering there is a significant association between diabetes and prothrombotic status, it could be responsible for the increased risk of thrombotic events with a worse prognosis.

The genotoxicity study of resveratrol in primary gastric adenocarcinoma cell cultures.

Gastric cancer is the second most common cause of cancer-related death in the world. Some studies indicate that polyphenolic compounds and antioxidants exert a protective action against gastric cancer. Among the polyphenolic compounds tested and proven effective against gastric cancer is resveratrol, a natural polyphenol present in red wines and various human food items. Resveratrol has been shown to suppress proliferation of a wide variety of tumor cells. We tested the genotoxic activity of resveratrol in primary cell cultures from gastric adenocarcinoma, obtained by mucosal biopsy at upper digestive endoscopy. The adenocarcinoma cells were analyzed for the presence of micronuclei at different concentrations of resveratrol at 48 hours and at 72 hours. The results showed that resveratrol induced micronuclei dose-dependently. The frequency of micronuclei increased progressively with the dose of resveratrol used, the high frequency is in the primary culture initiated from gastric adenocarcinoma: signet ring cell type. The high frequency of micronuclei is at 72 hours at the 20 microg/mL resveratrol and is decreased at low concentrations (5 microg/mL, 10 microg/mL resveratrol). This results show the genotoxic activity of resveratrol in adenocarcinoma gastric cell and the anticancer property of this substance.

Pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder of connective tissue, characterized by elastic fibers mineralization and fragmentation, and affects the skin, eyes, cardiovascular system, and gastrointestinal system. PXE is caused by mutations in the ABCC6 gene, located on chromosome 16p13.1. We investigated clinical and laboratory three patients with pseudoxanthoma elasticum. All the patients present on dermatological examination yellowish papules, located especially on the neck and axillary area. In case no. 2 the patient presents "cutis laxa" in the axillary area. In case no. 3 the patient presents hyperpigmented spot on right forearm and another maculo-pigmented oval spot located at the base of the left posterior hemithorax. In two cases, the ophthalmologic examination shows angioid streaks. The modifications of elastic fibers (thickened or fragmented) are present in all cases.

Drug-induced hepatitis - morphological and ultrastructural aspects.

Frequency of drug-induced liver diseases is increasingly, more than 200 different drugs being incriminated in hepatic disorders. We performed a retrospective study on 65 cases of deaths due to drug intoxications and an experimental model of subacute hepatitis induced by acetaminophen. In our experimental model, we observed various histological lesions: granular degeneration, vascular congestion, lymphoplasmocyte infiltration, cytonecrosis. Histological criteria are not specifically, but very usefully, because based on these criteria we can suspect a drug etiology in hepatic disorders when any other cause is absent. Ultrastructural study of hepatocytes revealed some modifications, in addition to data provided by optical microscopy.

The endoscopic and morphological forms of early gastric cancer.

The early gastric cancer is an endoscopic notion in which gastric cancer is strictly placed to mucosis and submucosis without extensive manifestations. It is the form with favorable prognosis and better survival at 5 and 10 years. Our study tries to systematize the debut forms of early gastric cancer and their association with the lesions with malignisation risk. We also try to evaluate the incidence of endoscopic and histopathologic forms of early gastric cancer found in an internal medicine division. Our study included 435 patients with gastric cancer endoscopic and histologic diagnosed. Statistically, 64.36% were men and 35.64% were women, the mean age 48 +/- 7 years. The endoscopic forms of early gastric cancer were type I: protruded in 19 cases, type II: superficially in eight cases, type III: excavated in six cases. Early gastric cancer is diagnosed with difficulty, it represents in 7.58% of the gastric cancer, being most frequently asymptomatic. The endoscopic forms frequently found in early gastric cancer in the population were type I: protruded and type IIa: superficially elevated. The histopathological examination is compulsory at this form of gastric cancer, while in advanced gastric cancer endoscopy is often sufficient for diagnosis. Analysing the histopathological results of cases diagnosed with early gastric cancer we found: 22 cases with intestinal type and 11 cases diffuse type. Microscopically, 15 were intramucosal and 18 had submucosal invasion. I and IIa lesions were predominantly located at the antrum and are histologically differentiated adenocarcinoma. Differentiated carcinoma frequently produces an elevated lesion and the border is well demarcated. There are frequent opportunities to detect gastric cancer in the early phase and the patient can expect a complete cure by the surgical operation or endoscopical mucosal resection.

The importance of BMP6 marker within the process of epithelial-mesenchymal transition in the pleomorphic adenoma of the salivary gland.

The pleomorphic adenoma is the most frequently encountered tumor of the salivary glands, representing between 45% and 75% of the total number of the tumors of the salivary glands. According to the literature, there are many studies on the immunohistochemical aspects of the myoepithelial cells, present in the pleomorphic adenoma of the salivary gland. A big diversity of mono and polyclonal antibodies, such as the cytokeratins, muscular proteins and other markers, has been used. In our study, we investigated the immunohistochemical aspect of bone morphogenetic protein 6 (BMP6) marker concerning 15 cases of pleomorphic adenomas of the salivary glands. In the immunohistochemical study, we used the paraffin blocks that served for obtaining the sections necessary for the classical histopathological processing by means of the usual stainings. The immunohistochemical study used the enzymatic detection and the LSAB 2 (Labeled Streptavidin-Biotin 2) System technique as the working method. In order to underline the process of epithelial-mesenchymal transition, we also used double sequential immunohistochemical reactions. By the use of the BMP6 marker, we intended to evaluate the reactivity of the various tumor components in the pleomorphic adenomas of the salivary gland, for this marker, taking into consideration its possible involvement in the process of the epithelial-mesenchymal transition. The maximum reactivity for BMP6 was recorded at the level of the normal, excretory, intratubular units, in the luminal cells of the proliferative ductal units, in the myxoid matrix, the cytoplasm of the myxoid stellate cells and the plasmacytoid matrix and the cytoplasm of the chondroid lacunar cells. Some of the cells belonging to the solid, proliferative areas, some of the abluminal cells, that are part of the proliferative ductal units and certain myxoid stellate or plasmocytoid cells contain the S100 protein, which would indicate the existence of some processes of mesenchymal epithelial÷myoepithelial transdifferentiation in the development of this type of salivary tumor. The BMP6 expression is specific to the serous acini salivary cells, which are the most specialized epithelial salivary gland cells. The study demonstrated that the mesenchymal epithelial÷myoepithelial potential of transdifferentiation of the luminal cells that make up the proliferative units is certified by the immunohistochemical expression of some BMP6 purely mesenchymal protein cells.

The association between chronic pancreatitis and the iNOS-2087A>G polymorphism.

INTRODUCTION: Chronic pancreatitis is morphologically characterized by ductal dysplasia, breeding grounds for the proliferation of the ductal cells, the degenerative changes in pancreatic acinar cells and fibrosis, and it is defined on the basis of the clinical, morphological and functional criteria. AIM: The aim of our study is to examine the existence of a possible correlation between the iNOS-2087A>G polymorphism and chronic pancreatitis by means of the genetic analysis. MATERIAL AND METHOD: We have conducted the study at the Gastroenterology Clinic and the Research Center of Gastroenterology and Hepatology of the University of Medicine and Pharmacy, Craiova, between March 2015 - September 2016. The study had a prospective character. Both for the 58 patients diagnosed with chronic pancreatitis and for the 132 patients in the witness group, the biological material was represented by blood, (around 2.5 - 5 milliliters of venous blood) let on EDTA and kept at 4°C up to the separation of the DNA molecule. All the patients were genotyped for the iNOS - 2087A>G polymorphism, by means of the Real Time PCR technique with TaqMan probes. RESULTS: Analysing the prevalence of the iNOS genotypes within the study group and witness group, we have noticed that, statistically speaking, there are no significant differences between the two groups. CONCLUSION: As a conclusion, in the study lot we can sustain that the risk of developing chronic pancreatitis is not increased by the presence of the iNOS-2087A>G polymorphism.

Hepatorenal Syndrome: Diagnosis and Treatment - newsreel.

Hepatorenal syndrome (HRS) is defined as renal failure that occurs in the presence of severe acute or chronic liver disease in the absence of underlying renal pathology. Due to the functional nature of the disease and the absence of specific diagnostic markers, HRS diagnosis is determined based on positive criteria associated with excluding other causes of renal failure in patients with liver cirrhosis and ascites. Differentiation from other types of acute or chronic renal disease is extremely difficult and therapeutic options are limited, prophylactic behavior is most appropriate in patients with severe hepatic disease and risk factors for the installation of hepatorenal syndrome. Highlighting all precipitating factors of acute renal insufficiency and therapeutic modalities in order to minimize adverse events is an important step in improving the follow-up of the patients with liver cirrhosis. The prognosis is reserved especially for type 1 HRS. Liver transplantation is the best option for patients without contraindications. The therapies introduced in recent years, such as vasoconstrictor drugs or transjugular intrahepatic portosystemic shunt are effective methods in the renal function improvement.

Hyponatremia - unfavourable prognostic factor in hepatic cirrhosis.

Hyponatremia is defined by a level of Na in serum below or equal to 136 mEq/L while in hepatic cirrhosis it is classically considered as relevant only at a level of Na below 130 mEq/L. Hyponatremia frequently occurs in patients with end-stage hepatic disease. The frequency and severity are variable but it has been estimated that it occurs with a frequency of 57% in hospitalized patients with cirrhosis and in those on waiting lists for hepatic transplants. Signs and symptoms of hyponatremia are related to dysfunctions of the central nervous system, due to migration of the water from intravascular space to the brain cells, resulting in the occurrence of cerebral edema. Therapeutic options in hyponatremia are limited and are based on restriction of water consumption, exclusion of diuretics and vaptans. Hepatic transplant remains the only definitive treatment for end-stage hepatic diseases in which hyponatremia has occurred.

Psychosocial issues in patients with chronic hepatitis B and C.

Psychosocial issues and the quality of life are important components at the patients diagnosed with chronic hepatitis B and C. In function of the severity of the infection with virus B or the patients who already have cirrhosis, the treatment and psychosocial education should be improved because they have bigger problems. The frequency of psychosocial disorders seems to be raised at the patients diagnosed with chronic hepatitis B. Factors as alcohol abuse and a low social support have a negatively impact above mental health of these patients. The prevalence rate of chronic hepatitis C infection at patients with severe mental illness can be nine times higher than in healthy population. Usually patients with chronic hepatitis B have a quality of life and a mental health better than patients with chronic hepatitis C. Patients with psychiatric affections (especially institutionalized people) have generally a higher risk of being infected with virus B in comparison with general population. Patients with chronic hepatitis B and C suggest a higher grade of stigmatization from society. Despite clinical challenges which treatment with interferon at patients with chronic hepatitis and comorbidities represents, recent studies indicate the fact that treatment can be administrated in safe conditions at patients with viral chronic hepatitis and psychiatric disorders.

E-cadherin and α-SMA expression in the epithelial-mesenchymal transition of salivary glands pleomorphic adenomas.

The pleomorphic adenoma, known also as mixed tumor of epithelioma with reshuffling stroma, is the most frequent salivary gland tumor, representing 45-75% of the total salivary gland tumors. In our study, we have investigated the immunohistochemical expression of E-cadherin and alpha-smooth muscle actin (α-SMA) in 15 cases of pleomorphic adenoma of salivary glands. We noticed the constant presence of E-cadherin reactivity at the level of luminal cells that cover the proliferative structures of ductal-cystic type, which gradually disappears to the periphery. At the level of epithelial proliferative solid areas, the reactivity for E-cadherin was inconstant and heterogeneous, while α-SMA expression increased. This aspect indicated the involving of epithelial-mesenchymal transition process in the evolution of pleomorphic adenoma.

Histopathological study of pleomorphic adenoma of salivary glands.

The pleomorphic adenoma, also known as mixed tumor, presents an epithelial and mesenchymal histological structure, being also called epithelioma with altered stroma. The pleomorphic adenoma has a frequency of 70% of major salivary gland tumors, being located preponderantly at the level of parotid gland (52-84%), at the level of submandibular glands (7-17%) and at the level of the other salivary minor salivary glands (3-8%). The purpose of our study was the histopathological analysis of 45 cases of pleomorphic adenoma. The tumors were characterized by an increased structural pleomorphism, given by the multitude of cytological differences and proliferation patterns, and on the other side by the diversity of stromal component.

Acute trenant pneumonia of possible bacterial etiology.

A 48 years old, smoker (20 cigarettes/day), without known personal pulmonary antecedents, is presented in the emergency service accusing: dry cough, fever (38,8°C), chills, dyspnea at medium efforts, dizziness, symptoms occurred 4 days ago and gradually accelerated. Following the paraclinical tests two possible major differential diagnoses take shape: bacterial pneumonia and lung cancer. For the diagnosis of pneumonia pleads clinical appearance (fever, chills, cough) and the results of radiological examination. The diagnosis of bronchopulmonary tumor is denied by bronchoscopy, the PBTT which doesn't reveal tumor cells and clinically well evolution. The case is interpreted as a form of trenant bacterial pneumonia in slow resorption - for this pleads the favorable clinical and radiological evolution, broad-spectrum antibiotic therapy, balancing electrolyte.

Serum and tumor microenvironment IL-8 values in different stages of colorectal cancer.

INTRODUCTION: Colorectal cancer represents a major cause of mortality and morbidity and occupies the third place as cancer incidence and the fourth place as cancer mortality. Colorectal cancer causes 608 000 deaths per year, despite correct applied treatment (surgery and chemotherapy). Interleukin 8 (IL-8) is an important proinflammatory cytokine with an important role in leukocyte chemoattraction. IL-8 also represents an important tumorigenic and proangiogenic factor. MATERIALS AND METHODS: We have studied 68 patients aged between 55 and 70 years, hospitalized in the IInd Surgery Clinic of the Emergency County Hospital of Craiova, Romania. According to TNM grading, the patients were in stages II, III and IV. From these patients, we have prelevated two types of samples: serum and tumor fragment. RESULTS: IL-8 values were significantly increased, both in serum and tumor supernatant. The highest IL-8 values were found in tumor supernatant and in advanced stages; IL-8 increased values were correlated with tumor growth and TNM stage. CONCLUSIONS: IL-8 has an important role in colorectal cancer growth and metastasis and represents an important therapeutic target in this type of cancer. IL-8 represents also a predictor for colorectal cancer prognosis.

The role of immunohistochemistry in diagnosing a synchronous colon tumor.

Simultaneous presence of an epithelial and lymphoid tumor of the digestive tract is quite rarely met in literature. In this paper, we describe a case which presented such an association. Diagnosis was established by histological study, followed by immunohistochemistry. It is a synchronous colon tumor, associating a non-Hodgkin's lymphoma to a colon adenocarcinoma. The 57-year-old male patient has been clinically diagnosed with a tumor of the left abdominal quadrant and paraclinically (imaging and endoscopic) with colon neoplasm. Exploratory laparotomy revealed two tumors: one tumor of five centimeters in the sigmoid, with firm consistency, mobile on lower plans and the second tumor in the ceco-ascending colon, measuring about 7 cm, irregular, with firm consistency, mobile on lower plans, with lymph nodes extending to retroperitoneal space. The urinary bladder, kidneys, liver and stomach were of normal aspect. Subtotal colectomy was performed with latero-lateral ileo-sigmoid anastomosis. Microscopic examination revealed sigmoid tumor as G1 adenocarcinoma and cecal tumor as B-cell type lymphoma. Immunohistochemistry established the final diagnosis of cecal localization being a diffuse immunoblastic large B-cell non-Hodgkin's malignant lymphoma. The final diagnosis of this patient was actually a synchronous manifestation of a colon adenocarcinoma and non-Hodgkin's lymphoma. This association puts into question synchronous tumors etiopathogeny matter.

Fibroepithelial polyps - a rare pathology of the upper urinary tract.

Ureteral fibroepithelial polyps are a rather uncommon pathological entity. However, an increase of their incidence was recorded during the recent period, probably due to better access to the investigative methods. The aim of this study was to assess the diagnosis and endoscopic treatment particularities of these cases. Our experience was based on 11 cases evaluated in the last 12 years. The mean patients' age was 43 years (between 26 and 54). Hematuria, flank pain, suprapubic discomfort and urinary frequency were the main symptoms. Diagnosis was based on ultrasonography, IVP (intravenous pyelography), cystoscopy and ureteroscopy and confirmed by histopathology. In four cases, smooth polypoid masses covered by apparently normal urothelium and protruding through the ureteral orifice were discovered. In six cases, the fibroepithelial polyps appeared as a large filling defect in the ureter. In another case, a large, organized, blood clot protruding from the left orifice imposed ureteroscopy with the identification of a mid-ureteral polyp. Ten cases were treated by ureteroscopic laser ablation, while transureteral resection was applied in one case. After complete excision of the polypoid base, a double-J stent was indwelled for six weeks. Histology described the lesions as fibroepithelial polyps: hyperplastic urothelium overlying an intact basement membrane with extensive submucosal edema, dilated blood vessels, chronic inflammatory cells and fibrous stroma. No recurrences were found during a follow-up period of 56 months (between 6 and 72 months). Ureteral fibroepithelial polyps represent a rare pathology, ureteroscopy being the gold standard diagnostic method. The appearance and location of the lesions are pathognomonic, and complete excision may be performed by ureteroscopic approach. Recurrences seem to be rare in these tumors.

The involvement of growth differentiation factor 5 (GDF5) and aggrecan in the epithelial-mesenchymal transition of salivary gland pleomorphic adenoma.

Pleomorphic adenoma is the most common salivary gland tumor with annual incidence of 2-3.5/100 000 in population. The histogenesis of salivary gland pleomorphic adenoma is still unclear. One concept sustains the existence of an epithelial-mesenchymal transitions (EMT) process in pleomorphic adenomas by which neoplastic epithelial cells transdifferentiate into mesenchymal cells and leading to tissue heterogeneity from this salivary gland neoplasia. Here we investigate by immunohistochemistry the expression of growth differentiation factor 5 (GDF5) and aggrecan in 15 cases of salivary gland pleomorphic adenomas. We found that both markers were present in normal salivary gland, mainly in the cells that line striated and intercalated ducts suggesting their involvement in the morphogenesis of this duct system. A constant positive reactivity for both markers was recorded in transition regions from tubular proliferative units to myxoid areas suggesting the involvement of an EMT process during the tumorigenesis of such salivary gland neoplasia. Also, both markers may be implicated in the transdifferentiation of neoplastic myoepithelial cells from the myxoid zones to lacuna cells of adjacent chondroid areas completing the morphology of this salivary gland tumor.