Colorectal Cancer: An Update on Treatment Options and Future Perspectives.

Throughout the years, colorectal cancer has steadily become a global health problem. While other types of cancers have seen a decline in cases because of screening and vaccination programs, colorectal cancer has risen become the third most diagnosed cancer worldwide and, more worryingly, the second leading cancer-related cause of death. The introduction of targeted therapy has been widely considered a major paradigm shift in the treatment of colorectal cancer, which agents such as bevacizumab and cetuximab quickly becoming mainstay options in the treatment of locally advanced or metastatic disease. However, this type of treatment has also shown its limitations, with limited or no benefit for a large portion of the patients. With more and more knowledge being gathered on the molecular mechanisms which govern the malignant phenotype presented by colorectal cancer, scientists are engaged in a continuous effort to develop new therapies based on these discoveries.

A Statistical Analysis of Risk Groups in Colorectal Cancer Patients.

Colorectal cancer (CRC) is considered a major global health concern due to an increasing number of new cases and cancer-related deaths each year, strong link to dietary habits prevalent in middle and high-income countries and limited therapeutic options especially in locally-advanced and metastatic settings. To counter this growing problem, the scientific community has strived to underpin the major molecular mechanisms behind the aggressive phenotype displayed by CRC and also develop new agents to selectively target and inhibit these core drivers. This evolution has allowed the separation of patients according to different risk groups in concordance with epidemiological parameters alongside novel biomarkers such as gene alterations, protein overexpression and aberrant signaling pathways. In this study we included 20 patients who underwent colonoscopy and were later received histopathologic confirmation of CRC. The statistical anamnestic data obtained from the patients (age, gender, home distribution, signs and symptoms) was corroborated with the results obtained from the histopathologic and immunohistochemical analysis of the samples obtained via colonoscopy. The average age was 63.8 years, the male: female ratio was 2.33 and the origin of 2/3 of the patients was urban and the most encountered symptoms were transit disorders (75%). In terms of colonoscopy results, the majority of tumors were found on the rectum (85%), 90% of tumors were adenocarcinomas, having a vegetant aspect in 60% of the cases and a moderate degree of differentiation in 50% of situations.

The Treatment of Arterial Hypertension.

Arterial hypertension is the leading cause of death worldwide and is one of the most important public health problems. Arterial hypertension is a major cardiovascular risk factor with an increasing incidence. In this paper we set out to analyze a group of 3050 patients hospitalized between January 2013 and December 2017 in terms of drug therapy. We found that the majority of patients received drug treatment with a converting-enzyme inhibitor as a monotherapy, and the most common drug association was the association between conversion enzyme inhibitor and calcium channel blocker.

Molecular phenotypes of the human kidney: Myoid stromal cells/telocytes and myoepithelial cells.

The connective stromal and epithelial compartments of the kidney have regenerative potential and phenotypic flexibility. A few studies have shown that cells appertaining to both compartments can exhibit myoid phenotypes. The purpose of our study was to investigate the myoid pattern of kidney and its association with the kidney niches containing stromal cells/telocytes (SC/TCs). We performed an immunohistochemical study using a panel of endothelial, myoid, mesenchymal and stem/progenitor markers, namely CD31, CD34, CD105 (endoglin), CD117/c-kit, nestin, desmin, α-smooth muscle actin (α-SMA) and the heavy chain of smooth muscle myosin (SMM). We used histologically normal kidney samples, obtained after nephrectomy, from nine adult patients. The capsular SC/TCs had a strong CD34 and partial nestin and CD105 immunopositivity. Subcapsular and interstitial SC/TCs expressed c-kit, nestin, CD105, but also α-SMA and SMM, therefore having a myoid phenotype. The endothelial SC/TCs phenotype was CD31+/CD34+/CD105+/nestin±/SMM±/α-SMA±. All three myoid markers were expressed in periendothelial SC/TCs. We also found a scarce expression of nestin in parietal epithelial cells of Bowman's capsule, and in podocytes. In epithelial cells, we found a positive expression for CD31, CD117/c-kit, desmin, CD34, SMM, and CD105. In epithelial tubular cells, we found a predominant basal expression of the myoid markers (SMM and desmin). In conclusion, myoepithelial tubular cells, myoid endothelial cells and myoid SC/TCs are normal constituents of the kidney.

Urinary Bladder Tumors Clinical and Statistical Retrospective Study.

Nowadays, urinary bladder cancer represents a major health problem, due to very high medical and social costs. This disease affects mainly the elderly. We performed a study on 1073 patients admitted to the Urology Clinic within the Emergency Clinical Hospital of Craiova, between 2013-2015 with bladder cancer. Of the 1073 cases, 741(69.06%) were diagnosed in men, and 332 (30.94%) were found in women, the men/ women ratio being of 2.23/1. The highest incidence of bladder tumors was recorded in individuals aged between 60 and 79 years old. In this age group, there were admitted 734 patients with bladder cancer, representing 68.44%. Regarding the tumor recurrence, out of 1073 bladder tumors, a number of 608 (56.66%) patients were diagnosed with primary tumors, while a number of 465 (43.34%) patients presented recurrent tumors. Of the symptoms presented by the patients, the most frequent were haematuria (present in about 87% of the patients), pollakiuria (present in 64% of the patients), dysuria (present in 55% of the patients) and urinary infections (present in about 23% of the patients).

Subsets of telocytes: Myocardial telocytes.

Telocytes (TCs) are morphologically defined as small-sized cells with long, thin, moniliform processes called telopodes (Tps). Numerous papers imply that TCs are a distinctive cell type, and that transmission electron microscopy (TEM) is the gold standard tool for their identification. We aimed to reproduce previous studies on myocardial TCs to check their validity. For this purpose we performed an immunohistochemical study on human cardiac samples from six autopsied donor cadavers, using antibodies against CD10, CD31, CD34, CD146, Ki67, alpha-smooth muscle actin (α-SMA), Platelet-Derived Growth Factor Receptor-alpha (PDGFRα) and laminin. Additionally we performed a TEM study on cardiac samples from three human autopsied donor cadavers and five adult Sprague-Dawley rats. We found endothelial cells (ECs), cords, and filopodia-projecting endothelial tip cells (ETCs) that expressed CD10, CD31, CD34, CD146, and PDGFR-α. Often, endothelial cells closely neighbored the sarcolemmal basal laminae. Endothelial progenitor cells, as well as nascent capillaries, were CD31+/CD34+. Proliferative endothelial cells expressed Ki67. In larger vessels we found pericytes that expressed CD146 and α-SMA; scarce α-SMA-expressing spindle-shaped cells lining cardiomyocytes were suggestive of a pericytic role in angiogenic sprout guidance. The TEM study showed that endothelial tubes are almost exclusively found in the narrow myocardial interstitia. ECs that built them up appeared identical to the cells that previous TEM studies have suggested to be myocardial telocytes. A subset of stromal cells with TC-like phenotype and telopodes-like processes actually seem to configure blood vessels, and therefore belong to the endothelial lineage. This study shows that data presented in previous studies on myocardial telocytes is not enough to allow the reproducibility of the results. At least a subset of cells considered to be TCs might belong to the endothelial lineage.

Repeated Events of Acute Ischemic Stroke in a Patient with Essential Thrombocythemia.

Essential thrombocythemia (ET) represents a risk factor for ischemic stroke, although it is a rare cause. Chronic myeloproliferative disorder is associated with proliferation of megakaryocytes sustained increases circulating platelet count. Essential thrombocythemia cause is not known, yet, many patients suffering from this disease may have no symptoms for a long time. Early detection is necessary because it may recur frequently thrombosis if not treated properly. We present a case of a 72 year old man with a history of three stroke events. The clinical diagnostic procedure revealed an increased platelet count was 961000/ml, and these cerebrovascular events were the first manifestation of essential thrombocythemia.

Clinical, Epidemiological and Etiopathogenic Study of Ischemic Stroke.

INTRODUCTION: We conducted a retrospective study on patients who were diagnosed with ischemic stroke and hospitalized in Neurology I Neuropsychiatric Hospital of Craiova, Romania, between 2010-2014. We based our study on 6391 patients admitted with ischemic stroke. MATERIAL AND METHODS: We evaluated patients based on demographic data (age, sex, environment); neurological and cardiological examination; risk factors and comorbidities. RESULTS: After analyzing the results the most of the pacients included in our study by origin of country, most of them were from rural areas (61%-4201 cases), and the rest were from urban areas (39%-2730 cases). From the risk factors the most common was high blood pressure present in about 70% of all patients. The most common etiopathogenic mechanism was due to cerebral artery thrombosis 86% followed by cerebral artery embolism 11%. CONCLUSIONS: The high blood pressure was found to be significantly associated with risk of ischemic stroke. Regarding etiopathogenicity in our study cerebral artery thrombosis was present in most cases.

Correlation between Immunohistochemical Subtype and Clinicopathological Features in Patients with Diffuse Large B-cell Lymphoma.

The aim of this study was to establish correlations between certain clinical, biological, therapeutic factors and diffuse large B-cell lymphoma (DLBCL) subtypes. For this purpose, between January 2007 and December 2016 a total number of 97 patients with de novo diffuse large B-cell lymphoma were analyzed. Patients with a high prognostic index and non-GCB DLBCL positively correlated and exhibited lower survival rates than low IPI, GCB patients. IPI scoring system and cell-of-origin classification should be used together as a single valid prognostic evaluation tool for DLBCL.

Therapeutic Options in Diffuse Large B-Cell Lymphoma - A Retrospective Study and Review of the Literature.

The aim of this retrospective study was to assess the differences between standard R-CHOP and other Rituximab-associated chemotherapy (R-miniCHOP and R-CHOEP) regimens in terms of survival and potential adverse effects. The six-month survival outcomes of 94 diffuse large B-cell lymphomas (DLBCL) patients indicated no statistical difference between overall survival and disease-free survival in the two subgroups. The biological response to therapy (blood count, LDH levels) was similar in both subgroups. Despite having different clinical indications, R-miniCHOP and R-CHOEP provide viable therapeutic alternatives to the standard R-CHOP regimen.

Embryonic hematopoietic stem cells and interstitial Cajal cells in the hindgut of late stage human embryos: evidence and hypotheses.

There have been few studies on human embryos describing a specific pattern of hindgut colonization by hematopoietic stem cells (HSCs) and interstitial Cajal cells (ICCs). We aimed to study CD34, CD45 and CD117/c-kit expression in late stage human embryos, to attain observational data that could be related to studies on the aorta-gonad-mesonephros (AGM)-derived HSCs, and data on hindgut ICCs. Antibodies were also applied to identify alpha-smooth muscle actin and neurofilaments. Six human embryos of 48-56 days were used. In the 48 day embryo, the hindgut was sporadically populated by c-kit+ ICCs, but, in all other embryos, a layer of myenteric ICCs had been established. Intraneural c-kit+ cells were found in pelvic nerves and vagal trunks, suggesting that the theory of Ramon y Cajal assuming that ICCs may be primitive neurons may not be so invalid. Also in the 48 day embryo, c-kit+/CD45+ perivascular cells were found along the pelvic neurovascular axes, suggesting that not only liver, but also other organs could be seeded with HSCs from the AGM region. CD45+ cells with dendritic morphologies were found in all hindgut layers, including the epithelium. This last evidence is suggestive of an AGM contribution to the tissue resident macrophages and could be related to processes of sprouting angiogenesis which, in turn, have been found to be guided by filopodia of endothelial tip cells. Further studies on human embryonic and fetal material should be performed to attempt to clarify whether the hindgut colonization with HSCs is a transitory or definitive process.

A Case of Bilateral Aseptic Necrosis of the Femoral Head.

Aseptic necrosis of the femoral head is a disease whose etiology is not completely elucidated and generally affects young adults aged between 30 and 50 years. In a significant number of patients bilateral disease occurs, which makes detection in its early stages constitute an important objective. We present the case of a male patient, aged 23 years, with the following risk factors: smoking and chronic alcohol consumption, who is diagnosed with aseptic necrosis of the left femoral head, ARCO stage IV, and in just six months after the diagnosis and hip arthroplasty, he suffers an injury which leads to the same diagnosis in the contralateral hip. We want to emphasize that for all patients with a high index of suspicion there should be an MRI examination, because the plane radiographs or CT are most often not relevant in detecting early signs of this condition. Diagnosis of aseptic necrosis of the femoral head in the early stages is a necessity in order to obtain an optimal result of conservative treatment.

Squamous cell carcinoma of the oral cavity: clinical and pathological aspects.

Oral cavity cancer is a public health problem as the sixth leading cause of cancer worldwide. Most tumor lesions are detected in stage III and IV, leading to a poor prognosis, five-year survival rate ranging between 10% and 40%. Oral cancer etiology is multifactorial, known still incomplete. The main etiopathogenic factors are exposure to cigarette smoke and alcohol consumption. We conducted a retrospective study of oral cavity tumors hospitalized in 2008-2012 in Oral and Maxillofacial Surgery Clinic of the Emergency County Hospital of Craiova, Romania. Of 143 tumors of the oral cavity, 125 were malignant, and of these, 115 (92%) were represented by squamous cell carcinoma. Tumor lesions were more common in males (69%), patients from rural areas (64%) and those over 50-year-old (87.71%).

Comparative study of microvascular density in experimental third-degree skin burns treated with topical preparations containing herbal extracts.

During the healing process of third-degree skin burns, a very complex response involves different cells and tissues linked together by intra- and extra-cellular mechanisms. For the restoration of damaged tissues, angiogenesis is the key point in the formation of new blood vessels. By their emollient, astringent, antiseptic, anti-inflammatory, biostimulator, epithelizing and cicatrizing effect, active principles from natural products contribute to the acceleration of the wound-healing process. In our study, we investigated the angiogenesis process in experimental model of third-degree skin burns treated with three topical preparations (cold-creams) containing 10% herbal extracts, comparing with 1% sulfadiazine cream and cold-cream base respectively. By their biostimulator, epithelizing and cicatrizing effect, cold-creams with herbal extracts are locally modulators of the cellular response and support the wound healing. The phytocomplex stimulates the favorable evolution of the burnt skin wounds and the development of neoangiogenesis capillaries.

Phases of the cutaneous angiogenesis process in experimental third-degree skin burns: histological and immunohistochemical study.

Skin burns represent a major problem of public health because of their frequency and because of their seriousness, too. The healing process of the burnt wound is extremely complex, as it requires a well-coordinated collaboration among different tissues and cellular strings. From the morphological point of view, the stages of the repairing process of the skin wounds include processes of inflammation, proliferation and tissular remodeling. Angiogenesis has a role of extreme importance within the healing process of third-degree skin burns. That is because the vascularization remake is necessary for feeding the tissue of granulation with nutritive substances and oxygen. The angiogenesis started relatively fast. Three days after the producing of the burn, there could be identified strings of CD34+ endothelial precursor cells at the edges and deep into the wound, all these having contact with the normal blood vessels or with those lees affected by the thermal aggression. After the lumenization of the newly-formed capillary vessels, there appeared the pericytes within their membrane. The CD34+ endothelial precursor cells (EPc), as well as the pericytes, participate at the synthesis of the base membrane of the angiogenesis vessels. The density of the angiogenesis vessels on the surface unit within the tissue of granulation grew from three to 12 days. After that, they reduced progressively while the tissue of granulation was becoming mature. The angiogenesis vessels go through a process of reshuffling and maturation at the same time with the maturation of the tissue of granulation, but these processes did not appear to be finished when the skin was completely healed, and the epidermis was totally recovered.

The effect of ultraviolet radiation on the cornea - experimental study.

Ultraviolet (UV) radiation in high doses may have harmful effects on the eye. The sources of UV radiation are the sun, as well as some artificial sources such as UV lamps or voltaic arcs. Chronic exposure to UV can cause damage to the anterior pole of the eye, ranging from minor (pterygium) to serious photokeratitis. In our study, we applied a UV dose of 6.5 J/cm(2) in the wavelength range of 290-400 nm, for five consecutive days per rat anterior pole of the eye. Seven days after the last dose of radiation, the animals were sacrificed, harvesting both the irradiated and the non-irradiated eye. Histological and immunohistochemical examination of the lesions revealed that the greatest damage to the epithelium was recorded prior to and 2/3 of the remaining corneal stroma. The epithelial lesions we found varied from pseudokeratosis and detachment of the Bowman epithelium membrane to deep epithelial necrosis. Within the corneal stroma, we observed the formation of interstitial edema with disruption of the collagen structure. We also noticed the presence of an inflammatory infiltrate composed mainly of lymphocytes and CD68+ and CD163+ macrophages, as well as the occurrence of vascular devices. These consisted of angiogenesis capillaries with structured wall composed mainly of endothelial CD34+ precursor cells and a basal membrane rich in collagen IV fibers.

Microscopic aspects of pulpal changes in patients with chronic marginal periodontitis.

Chronic periodontitis is one of the most frequent and severe diseases involving the tooth. Untreated, they can lead to tooth loss. Our study involved 67 patients with chronic marginal periodontitis who underwent tooth extraction, of which 29 had moderate periodontal lesions and 38 severe periodontal lesions. The microscopic study of the dental pulp revealed significant changes in all patients. In patients with moderate periodontitis the pulp tissue was found to be the site of an enhanced process of collagenous fibrosis associated with a moderate inflammatory infiltrate, dystrophic mineralization, reduced blood vascularization and arteriolosclerosis. The dental pulp of patients with severe periodontitis showed an abundant chronic inflammatory infiltrate associated with pulpal necrosis, vascular congestion, microhemorrhages, dentin demineralization and odontoblast impairment.

Bony metaplasia in a caecum adenocarcinoma.

Ectopic bone formation in the digestive tract is a very rare phenomenon in pathology. Most cases of bone metaplasia were found in distal colon tumors, rectum and sigmoid respectively. We present a case of well-differentiated adenocarcinoma of the caecum (the second case of literature) associated with bone metaplasia, which debuted atypical, with symptoms of infectious enterocolitis, in a 72-year-old female patient, with no history of digestive pathology. Highlighting bone metaplasia was achieved by current histological techniques. Patient's evolution was favorable with surgical treatment and chemotherapy.

Adverse effects of peg-Interferon and Ribavirin combined antiviral treatment in a Romanian hepatitis C virus infected cohort.

INTRODUCTION: Adverse effects appearing during combined peg-Interferon and Ribavirin antiviral treatment against chronic infection with the hepatitis C virus are a major cause for treatment failures and abrupt interruption. In the prospect of the imminent introduction of new direct acting antiviral agents, with demonstrated higher rates of adverse effects, our study aimed to assess the severity and incidence of several types of adverse effects in a cohort of genotype 1 infected Romanian patients. MATERIALS AND METHODS: We prospectively included a total of 150 patients (45 men), aged 25 to 64 years, who received combined peg-Interferon and Ribavirin antiviral treatment for chronic hepatitis C. Out of these, 145 patients also had liver biopsies prior to treatment initiation. We recorded their viral loads, hemoglobin values and thrombocyte counts, as well as any dermatological, psychiatric or constitutional adverse effect after twelve doses, eight and twelve months of treatment, with two follow-up examinations at three and six months after treatment completion. RESULTS: Viral loads significantly decreased after 12 doses of treatment, in the end a total of six patients (two men and four women) being declared non-responders. Hemoglobin values and thrombocyte counts significantly decreased during treatment (p<0.0001), with their values being restored to pre-treatment levels during the follow-up period. We did not find significant differences between the 12-doses, 8 and 12 months values during treatment (p>0.05). We recorded 43 cases (11 men and 32 women) presenting with rashes, drug eruptions and erythema. We only encountered grade 1 and 2 dermatological adverse effects. Psychiatric effects were present in 34 cases (10 men and 24 women, 22.6% of the group) and manifested as mild depressions, which did not require specific medication or antiviral dose adjustment. Patients also presented headaches (80.6%), fatigue (71.3%), nausea (47.3%), arthralgias (35.3%) and fever (30%). CONCLUSIONS: We did not encounter severe hematological adverse effects that would require Ribavirin dosage adjustments. Cutaneous and psychiatric adverse effects were also present in a significant number of patients; however, their severity did not influence the continuity or outcome of the antiviral treatment. Other constitutional effects were also present with no direct consequence on the course of treatment. Future agents employed in antiviral therapy shall require extensive monitoring of all adverse effects already acknowledged during dual combination therapy.

Macroscopic and microscopic findings in avascular necrosis of the femoral head.

UNLABELLED: The avascular necrosis of the femoral head is an illness induced by the cutoff of blood flow to the femoral head and it affects mostly young adults between the ages of 30 and 50 years, raising therapeutic and diagnostic issues. Many risk factors are incriminated in the development of avascular necrosis of the femoral head like: trauma, chronic alcohol consumption, smoking, administration of corticosteroid drugs, most of the cases are considered to be idiopathic. The main goal of our paper is to describe the macroscopic and microscopic variations of the bone structure, which occur in patients with avascular necrosis of the femoral head. MATERIALS AND METHODS: The biological material needed for our study was obtained following hip arthroplasty surgery in 26 patients between the ages of 29 and 59 years, which previously were diagnosed with avascular necrosis of the femoral head and admitted in the Orthopedics Department of the Emergency County Hospital of Craiova (Romania) between 2010 and 2011. From a macroscopic point of view, we found well defined areas of necrosis, most of which were neatly demarcated of the adjacent viable tissue by hyperemic areas, loss of shape and contour of the femoral head and transformations of the articular cartilage above the area of necrosis. When examined under the microscope, we found vast areas of fibrosis, narrow bone trabeculae, obstructed blood vessels or blood vessels with clots inside, hypertrophic fat cells, bone sequestration but also small cells and pyknotic nuclei. The microscopic and macroscopic findings on the femoral head sections varied with the patients and the stage of the disease.