Evaluation of CD10 expression as a diagnostic marker for colorectal cancer.

Aim: We aimed to determine the potential of CD10 as a marker for the early diagnosis of adenocarcinoma of the colon. Background: Adenocarcinoma is diagnosed in one out of 20 individuals in the USA and western European countries. Its prognosis and treatment depend largely on the severity of the disease at the time of diagnosis. Additional new biological markers are being sought that can help diagnose colon cancer at an early stage. One such marker present in both serum and tumor tissue is CD10. Methods: CD10 concentrations were tested by ELISA and immunohistochemistry in serum and tissue samples, respectively, from 113 patients diagnosed histopathologically and treated for adenocarcinoma of the colon. Additionally, the ROC curve with optimal cut-off point based on Youden's criterion was calculated for CD10. Results: Serum concentrations of CD10 and its tissue expression in patients diagnosed with adenocarcinoma of the colon correlate with cancer staging based on the Astler-Coller-Dukes classification. To ascertain the optimal cut-off point for CD10 as a predictor of belonging to the study group, ROC curve was prepared for CD10. Optimal cut-off point for CD10 was 0.57, with prediction of belonging to the study group for CD10 ≥ 0.57. Conclusion: CD10 can be a useful marker in the early diagnosis of adenocarcinoma of the colon.

Immunogenetic, Molecular and Microbiotic Determinants of Eosinophilic Esophagitis and Clinical Practice-A New Perspective of an Old Disease.

Eosinophilic oesophagitis (EoE) is a chronic, allergic disease associated with a T-lymphocyte response inducing esophageal eosinophilic infiltration in the esophagus. Inflammation and tissue fibrosis are responsible for the main clinical symptoms such as food impaction and dysphagia. The etiopathogenesis is multifactorial in which genetic and environmental factors coexist. The most common trigger is a non-IgE-mediated food allergy to milk, wheat, egg, soybean, nuts, fish, and seafood. The second factor we focus on is the contribution of genetic variation to the risk of EoE, describing the expression profile of selected genes associated with eosinophilic oesophagitis. We raise the topic of treatment, aiming to eliminate inflammation through an elimination diet and/or use of pharmacologic therapy with the use of proton pump inhibitors or steroids and endoscopic procedures to dilate the esophagus. We demonstrate that early diagnosis and effective treatment prevent the development of food impaction and decreased quality of life. The increasing presence of EoE requires bigger awareness among medical specialists concerning clinical features, the course of EoE, diagnostic tools, and management strategies.

Peripheral T-Cell Lymphoma Possibly Due to Unrecognized Celiac Disease in an Elderly Patient: A Case Report.

Celiac disease (CD) is widely perceived as a childhood disorder. However, it has been demonstrated that 19-34% of new CD cases are diagnosed in patients over 60 years of age and lack the typical presentation. A 76-year-old female was admitted to the clinic due to a recurrent fever that had lasted over a year accompanied by progressive weakness, weight loss of about 10 kg, dehydration, and malnutrition. The patient had undergone resection of a fragment of the small intestine due to perforation and abscess 13 years previously (at which time no histopathological examinations were performed). During the current hospitalization, despite extensive laboratory, microbiological, and imaging tests, no specific diagnosis was made. Symptomatic treatment and empirical antibiotic therapy were conducted, but the patient died on the twenty-seventh day of hospitalization due to progressive respiratory failure. The autopsy revealed peripheral T-cell lymphoma in the mesentery of the small intestine, uterus, cecum, lung, and mediastinal lymph nodes. Based on the clinical picture, we believe that the lymphoma was induced by long-term, undiagnosed CD. Current knowledge allows us to see age-related differences in the manifestation of celiac disease and to be alert to the possible late-stage complications of the disease. The lack of awareness of how CD's symptoms vary with age may lead to misdiagnosis and serious consequences of delayed diagnosis, including death.

Home parenteral nutrition a life-saving therapy in a primary intestinal lymphangiectasia patient affecting the entire GI tract - 3 year follow-up case report.

INTRODUCTION AND IMPORTANCE: Primary intestinal lymphangiectasia (PIL) is a rare protein-losing gastroenteropathy of unknown etiology, characterized by impaired lymphatic vessels drainage. The pathological changes in PIL result in usually localized or diffuse dilatation of intestinal lacteals, leading to leakage of lymphatic fluid rich of proteins, lymphocytes, and immunoglobulins into the intestinal lumen. PIL may be asymptomatic or mildly symptomatic in moderate forms of the disease. In some patients, though, the outcome may be poor or even life-threatening. This case report demonstrates the severity of protein malnutrition, in some cases, and the extent of GI tract affected, requiring to start PN early and the need for its continuation as home parenteral nutrition (HPN). CASE PRESENTATION: We present a case of 39-year-old male with Factor V Leiden deficiency, who presented initially with symptoms of malnutrition and anasarca. The diagnosis was confirmed by histopathological findings pathognomonic for PIL from biopsies of the stomach, small intestine and colon. CLINICAL DISCUSSION: The patient was started on low fat, high protein parenteral nutrition from the beginning of the treatment and required a long-term HPN for 3 years, because trials of tapering off and discontinuation of PN led to worsening of the biochemical results and recurrence of symptoms. Patient gradually improved and stabilized with persistent nutritional support. CONCLUSIONS: The presented case report shows the magnitude of nutritional support (HPN) needed for severe PIL patients. HPN offers PIL patients with poor outcome and life-threatening complications a chance to improve and lead a normal life.

Usefulness of rebiopsy in the case of mesangial pathology.

Immunologically different types of glomerulopathies show varied symptoms and clinical courses. Unlike in lupus nephritis, repeated biopsy is rarely performed in cases of mesangial glomerulonephritis. We reviewed 200 cases wherein rebiopsy was performed in patients with diagnosed mesangial glomerular pathology over a 30-year period and analyzed the symptoms follow-up in these cases. Further, we evaluated the morphological changes between the first and final biopsies to identify cases of histological progression and histological remission and examined the correlation between such changes and clinical symptoms. The time between the first and last biopsies ranged from 7 months to 35 years. The most common for the initial biopsy was nephrotic syndrome, followed by non-nephrotic proteinuria; other symptoms occurred rarely. Histological progression occurred at various stages of observation, ranging from within a few months to after several years. Histological progression and remission were detected in 118 and 3 patients, respectively, whereas there was no difference in morphological findings between the first and last biopsies in 79 patients. Rebiopsy is useful in patients who do not respond adequately to treatment, and especially in those with increased clinical symptoms. Moreover, electron microscopic examination is necessary to discover early signs of histological progression.

Common sense and tumor treatment. A case of pilomatrical carcinoma in a 21-year-old patient with surprisingly rapid tumor progression.

Pilomatrical carcinoma is a rare tumor originating from skin appendages, usually occurring between the 5th and 7th decade of life. We present a case of an exceptionally young, 21-year-old patient with surprisingly rapid tumor progression and answer the question, what was the reason for such uncontrolled tumor growth. The main concern is the diagnostic challenge and a peculiar, one week race against time and tumor progression so that the least disfiguring surgery could be done.

Transcriptomic Profile of Genes Encoding Proteins Involved in Pathogenesis of Sjögren's Syndrome Related Xerostomia-Molecular and Clinical Trial.

Sjögren's syndrome (SS) is characterized by xerostomia. We aimed to investigate and compare gene expressions in the labial salivary glands of SS patients with xerostomia SS (sicca) and without xerostomia SS (non-sicca) and of healthy subjects (HS) by means of microarray analysis, and to find genes involved in xerostomia. The study group comprised 11 SS patients (3 SS (sicca) and 8 SS (non-sicca)) and 9 HS. The relative gene expression changes were validated with RT-qPCR in the larger study group. Among the differently expressed genes belonging to the "secretion" ontology group with a fold change >2 and with a p value < 0.05, the Transmembrane P24 Trafficking Protein 10 (TMED10), Protein Disulfide Isomerase Family A Member 4 (PDIA4), Calnexin (CANX), Amyloid Beta Precursor Protein (APP), and Transmembrane BAX Inhibitor Motif Containing 6 (TMBIM6) gene expressions in both SS (sicca) and SS (non-sicca) groups were lower than in HS. Significant correlations were observed between TMED10, PDIA4, and CANX gene expression in SS (sicca) patients compared to the controls. There were no differences between the SS (sicca) and SS (non-sicca) study groups in the expression of the aforementioned genes. Results indicate their role in the endoplasmic reticulum system, their overlapping function and the loss of the APP neuroprotective function in xerostomia. It has a multifactorial origin and can be triggered by disturbances to the various signaling pathways in saliva secretion.

Early presentation of sympathetic ophthalmia in optical coherence tomography studies: A case report.

Sympathetic ophthalmia (SO) is often diagnosed when an inflammatory process appears to be advanced. Herein, the authors present the prospective optical coherence tomography (OCT) study of the onset of SO in the sympathizing eye. Prior to any signs of uveitis, we noted the mild disintegration of the retinal pigment epithelium (RPE) layer, the interdigitation zone (IZ), and the ellipsoid zone (EZ). The complete disruption of IZ and EZ was seen 12 weeks later. After 14 weeks, the uveal inflammation was present, and OCT imaging disclosed the formation of nodule-like lesions between the Bruch's membrane and the RPE layer. The histopathological evaluation of the enucleated exciting eye confirmed the diagnosis of SO.

The influence of anti-TNF therapy on CD31 and VEGF expression in colonic mucosa of Crohn's disease patients in relation to mucosal healing.

INTRODUCTION: Immune-mediated angiogenesis may play an important role in the pathogenesis of inflammatory lesions in Crohn's disease (CD). The study aimed to assess the influence of anti-tumour necrosis factor (anti-TNF) therapy on the angiogenesis in relation to microscopic and endoscopic healing in CD patients. MATERIAL AND METHODS: Colonic tissue samples from 17 CD patients were taken during colonoscopy before and after anti-TNF therapy. Endoscopic and microscopic severities were estimated using validated scores. Immunohistochemical expression of CD31 and vascular endothelial growth factor (VEGF) were assessed in parallel. RESULTS: The expression of CD31 and VEGF decreased significantly after the anti-TNF therapy in parallel to endoscopic improvement; however, the microscopic activity did not change significantly. There was a correlation between the change in CD31 and VEGF expression (p = 0.01; r = 0.6), as well as endoscopic healing (p = 0.04; r = 0.4). CD31 immunoexpression correlated with the number of poly- and mononuclear cells in the infiltrates in the mucosal lamina propria before the therapy (p = 0.02; r = 0.5). CONCLUSIONS: We suggest that modulation of vascular proliferation can be a novel option to increase the efficacy of biological therapy in CD.

Usefulness of Endoscopic Indices in Determination of Disease Activity in Patients with Crohn's Disease.

Background. Assessment of endoscopic activity of Crohn's disease (CD) is of growing importance both in clinical practice and in clinical trials. The study aimed to assess which of the endoscopic indices used for evaluation of mucosal changes correlates with the currently used clinical indices for determination of disease activity and with the results of histopathological examination. Study. A group of 71 patients with CD and 52 individuals without a diagnosis of GI tract disease as a control group were investigated, considering clinical and histological severity of the disease and the severity of inflammatory changes in the bowel. Evaluation was conducted with the use of clinical, endoscopic, and histopathological indices. Endoscopic indices were then correlated with different clinical and histopathological indices with the aim of finding the strongest correlations. Results and Conclusions. Correlation between the clinical disease activity and the severity of endoscopic lesions in CD was shown in this study to be poor. The results also indicate that the optimal endoscopic index used in the diagnostic stage and in the assessment of treatment effects in CD is Simple Endoscopic Score for Crohn's Disease (SES-CD).

Applicability of endoscopic indices in the determination of disease activity in patients with ulcerative colitis.

OBJECTIVE: The combination of clinical remission and mucosal healing represents a major goal of different treatment strategies for ulcerative colitis (UC). This study aimed to assess which of the endoscopic indices used to evaluate mucosal changes in UC are correlated with clinical indices currently used to determine disease activity, as well as which of the endoscopic indices are correlated with the Geboes Index used for histological evaluation. It also aimed to find correlations between the currently used clinical activity indices and the histological Geboes Index. METHODS: A group of 49 patients with a confirmed diagnosis of UC and a group of 52 individuals without a diagnosis of gastrointestinal disease, who constituted the control group, were investigated. All patients were evaluated by colonoscopy, and the severity of mucosal changes was scored in terms of nine different endoscopic indices commonly used in both pharmacological trials and clinical practice. Evaluation was also carried out using clinical and histological indices. Endoscopic indices used for UC were then correlated with different clinical and histological indices to find the strongest correlations. RESULTS AND CONCLUSION: A high correlation was demonstrated between three of the 11 evaluated clinical indices - Improvement Based on Individual Symptom Scores, Ulcerative Colitis Disease Activity Index, and Schroeder Index - and all nine endoscopic indices - Ulcerative Colitis Endoscopic Index of Severity, Baron Score, Schroeder Index, Feagan Index, Powell-Tuck Index, Rachmilewitz Index, Sutherland Index, Lofberg Index, and Lemman Index. Improvement Based on Individual Symptom Scores was the index with the highest correlation with all the endoscopic indices used for UC. The above indices are recommended for clinical evaluation of UC activity. The Ulcerative Colitis Endoscopic Index of Severity was moderately correlated with a histological index, and it is therefore recommended for routine endoscopic mucosal evaluation in patients with UC.

Patterns of glomerular disease based on 4-year kidney biopsy material analyzed by light microscopy and immunofluorescence: a retrospective single-center analysis in Poland.

The aim of this study was to assess the epidemiology of different patterns of chronic glomerular diseases based on clinical, histopathological and immunofluorescent findings of glomerulonephritis patients hospitalized in the Department of Nephrology, Transplantology and Internal Diseases in Poznan between January 2009 and December 2012. We retrospectively studied 418 patients who had been subjected to renal biopsies. Data on serum creatinine concentration, 24 h proteinuria, arterial hypertension, diabetes mellitus, and histological and immunofluorescent findings were collected. The patients' mean age was 42 ±15. The male sex prevailed (53.1%). Immunoglobulin A nephropathy was the most common finding (18.9%), followed by focal segmental glomerulosclerosis (16.3%), membranous glomerulonephritis (10.1%), lupus nephritis (8.4%), extracapillary glomerulonephritis (3.3%) and membranoproliferative glomerulonephritis (2.6%). In 69 (16.5%) patients the biopsy was non-informative or non-diagnostic. Patients with membranous nephropathy presented the highest frequency of nephrotic syndrome (71.4%), followed by membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis. Combined analysis of the clinical, histopathological and immunofluorescent findings in glomerulonephritis patients based on a single center's data can provide important epidemiological findings.

Squamous cell lung cancer in a male with pulmonary tuberculosis.

Lung cancer and pulmonary tuberculosis (TB) are highly prevalent and representing major public health issues. They share common risk factors and clinical manifestations. It is also suggested that TB predicts raised lung cancer risk likely related to chronic inflammation in the lungs. However, it does not seem to influence the clinical course of lung cancer provided that it is properly treated. We present a case report of a 57-year old male with concurrent TB and lung cancer. He was diagnosed with positive sputum smear for acid fast bacilli (AFB) and subsequent culture of Mycobacterium tuberculosis. Besides, his comorbid conditions were chronic hepatitis C virus (HCV) infection and peripheral artery disease (PAD). Later while on anti-tuberculous treatment (ATT) squamous cell lung cancer (SCC) was confirmed with computed tomography (CT) guided biopsy. Due to poor general condition the patient was not fit for either surgery or radical chemo- and radiotherapy. He was transferred to hospice for palliative therapy. We want to emphasize that both TB and lung cancer should be actively sought for in patients with either disorder. In addition, there is no doubt that these patients with lung cancer and with good response to TB treatment should be promptly considered for appropriate anticancer therapy.

Disturbances in apoptosis of lamina propria lymphocytes in Crohn's disease.

INTRODUCTION: The aim of this study was to assess the potential mechanisms providing resistance to apoptosis of lamina propria lymphocytes (LPL) directlyin intestinal tissues from patients with Crohn's disease (CD). MATERIAL AND METHODS: Fifty CD patients were enrolled in the study. The control group consisted of healthy patients who underwent surveillance colonoscopy after endoscopic polypectomy. Each CD patient underwent colonoscopy with tissue sampling from inflamed areas of the colon with the assessment of immunohistochemical expression of active caspase 3, Fas, tumour necrosis factor receptor 1 (TNFR1), Bcl-2, Bax, CD4 and CD8. This was compared with healthy intestinal mucosa. RESULTS: The expression of active caspase 3 was significantly lower in LPL in CD (0.4 ±0.3 vs. 2.8 ±1.5; p = 0.0002). A statistically significant increase of CD4 and CD8 positive cells was noted in CD (2.3 ±0.5 vs. 1.2 ±0.2, p < 0.0001; 2.1 ±0.3 vs. 1.1 ±0.3, p < 0.0001, respectively). It was associated with a significant increase of the Bcl-2 (6.7 ±2.7 vs. 2.9 ±0.8; p < 0.0001) and a decrease of the Bax protein expression (3.4 ±2.1 vs. 5.5 ±1.8; p < 0.0001) in CD. The expression of Fas and TNFR1 did not differ between the study groups. CONCLUSIONS: LPL in CD are resistant to apoptosis when compared with physiological conditions. This is probably due to an imbalance in Bcl-2 family proteins. TNFR1-related pathway is probably not involved in disturbances of LPL apoptosis in CD.

Supplementary chromium(III) propionate complex does not protect against insulin resistance in high-fat-fed rats.

Improper eating habits such as high-fat or high-carbohydrate diets are responsible for metabolic changes resulting in impaired glucose tolerance, hyperinsulinemia, insulin resistance, and ultimately diabetes. Although the essentiality of trivalent chromium for humans has been recently questioned by researchers, pharmacological dosages of this element can improve insulin sensitivity in experimental animals and diabetic subjects. The aim of the study was to assess the preventive potential of the supplementary chromium(III) propionate complex (CrProp) in rats fed a high-fat diet. The experiment was conducted on 32 male Wistar rats divided into four groups and fed the following diets: the control (C, AIN-93G), high-fat diets (HF, 40% energy from fat), and a high-fat diet supplemented with CrProp at dosages of 10 and 50 mg Cr/kg diet (HF + Cr10 and HF + Cr50, respectively). After 8 weeks, high-fat feeding led to an increased body mass, hyperinsulinemia, insulin resistance, a decreased serum urea concentration, accumulation of lipid droplets in hepatocytes, and increased renal Fe and splenic Cu contents. Supplementary CrProp in both dosages did not alleviate these changes but increased renal Cr content and normalized splenic Cu content in high-fat-fed rats. Supplementary CrProp does not prevent the development of insulin resistance in rats fed a high-fat diet.

[Anterior commissure status in patients with larynx cancer]. / Stan spoidla przedniego u chorych na raka krtani.

AIM OF THE WORK: Assessment of directions and ways of cancer spreading in the anterior commissure of the larynx, depending on the tumor location, age, sex of patients in a clinical trial and in microscopic serial section study. MATERIALS AND METHODS: The study included 50 larynx preparations obtained from open partial and total laryngectomies (F-7; M-43). For the assessment of larynx anterior commissure microscopic status 28 larynx preparations with macroscopic free anterior commissure were used. For study of the directions and ways of tumor spreading in the anterior commissure served 22 larynx with macroscopic infiltration of anterior commissure. Anterior Commissure (AC) and TNM classifications was used to determine the location and tumor stage. Larynx anterior commissure was extracted and divided into 3 subregions: supraglottic, glottic and subglottic. RESULTS: The direction and the way of cancer propagation in larynx anterior commissure structures is dependent on morphological changes that occur with aging. Cancer spreads in the anterior commissure along the fibers anchoring voice muscle within the Broyles ligament and is seen in tumor cells microembolism. CONCLUSIONS: In patients with cancer of the larynx without macroscopically visible neoplastic lesions in the anterior commissure, cannot be excluded its microinfilration. Changed with age anterior commissure' Broyles ligament by the process of neovascularization and ossification is not an effective protection against the spread of cancer. Directions and the ways of cancer spread in the anterior commissure is similar in men and women. AC classification can be important in qualifying patients for organ preservation surgery and should be supplemented by an additional AC4 degree, taking into account subglottic changes in the anterior commissure of the larynx.

Anti-TNF antibodies do not induce the apoptosis of lamina propria mononuclear cells in uninflamed intestinal tissue in patients with Crohn's disease.

It is not known if anti-tumor necrosis factor (anti-TNF) agents provoke only apoptosis of lamina propria mononuclear cells (LPMC) engaged in inflammatory processes or whether it's a general phenomenon concerning all LPMC. In this study we carried out an immunohistochemical analysis of the expression of several apoptosis-related proteins (active caspase-3, Bax, Bcl-2, Fas, TNFR1, CD4, and CD8) in uninflamed mucosa in Crohn's disease (CD) patients treated with anti-TNF agents. 16 CD patients (mean age 34 ± 11, mean disease duration 7 ± 5 years) were included in the study. 10 patients were treated with infliximab and 6 - with adalimumab. The expression of active caspase 3, Bax, Bcl-2, Fas, TNFR1 and CD8 in LPMC did not change significantly after the therapy. We concluded that anti-TNF antibodies did not promote LPMC apoptosis in uninflamed tissues. This is in contrast to the phenomena observed in inflamed tissues. These data show that anti-TNF antibodies rather restore the susceptibility to apoptosis of LPMC in inflamed areas of the gut in CD, than directly induce LPMC apoptosis; otherwise the anti-TNF antibodies should have also induced apoptosis in the uninflamed mucosa.

Ki-67 and p53 expression in ileal pouches.

Development of dysplastic lesions that may potentially lead to cancer is sometimes reported within the ileal pouches. Dysplasia is in turn associated with increased expression of proliferation indices. The goal of this study was to evaluate the mitotic activity and possible expression of p53 in the epithelium within the ileal pouches in patients with chronic ulcerative colitis. The study involved archive material consisting of ileal pouches surgically removed from 17 patients diagnosed with ulcerative colitis. Several specimens were collected from each pouch. The immunohistochemistry (Ki-67 and p53 protein) control group (14 cases) consisted of the resection line specimens of colons removed due to colorectal adenocarcinoma. Intensity of the expression of the markers under study within the inflammatory infiltrates was assessed using a 5-point scale proposed by Berstein et al. Ki-67 expression was observed in all studied patients with marked intensity (Bernstein scale score +3, +4). Protein p53 expression was observed only in eight patients, and was mostly of low intensity (Bernstein scale score +1, +2). Immunohistochemical results confirmed the histopathological results that revealed dysplastic lesions, which are often an indication for radical procedures in ulcerative colitis patients. Our results suggest the usefulness of these examinations, also in the ileal pouch material.