Validation of the Appendicitis Inflammatory Response (AIR) Score.

BACKGROUND: Patients with suspicion of appendicitis present with a wide range of severity. Score-based risk stratification can optimise the management of these patients. This prospective study validates the Appendicitis Inflammatory Response (AIR) score in patients with suspicion of appendicitis. METHOD: Consecutive patients over the age of five with suspicion of appendicitis presenting at 25 Swedish hospital's emergency departments were prospectively included. The diagnostic properties of the AIR score are estimated. RESULTS: Some 3878 patients were included, 821 with uncomplicated and 724 with complicated appendicitis, 1986 with non-specific abdominal pain and 347 with other diagnoses. The score performed better in detecting complicated appendicitis (ROC area 0.89 (95% confidence interval (CI) 0.88-0.90) versus 0.83 (CI 0.82-0.84) for any appendicitis, p < 0.001), in patients below age 15 years and in patients with >47 h duration of symptoms (ROC area 0.93, CI 0.90-0.95 for complicated and 0.87, CI 0.84-0.90 for any appendicitis in both categories). Complicated appendicitis is unlikely at AIR score <4 points (Negative Predictive Value 99%, CI 98-100%). Appendicitis is likely at AIR score >8 points, especially in young patients (positive predictive value (PPV) 96%, CI 90-100%) and men (PPV 89%, CI 84-93%). CONCLUSIONS: The AIR score has high sensitivity for complicated appendicitis and identifies subgroups with low probability of complicated appendicitis or high probability of appendicitis. The discriminating capacity is high in children and patients with long duration of symptoms. It performs equally well in both sexes. This verifies the AIR score as a valid decision support. Trial registration number https://clinicaltrials.gov/ct2/show/NCT00971438.

Goblet cell carcinoid of the vermiform appendix - a case report.

Goblet cell carcinoid (GCC) is a rare neuroendocrine tumor of the vermiform appendix with uncertain clinical behavior. It was first described by Gagné and Subbuswamy in 1969 and 1974, respectively. The tumor occurs almost exclusively in the vermiform appendix. We present a case of a 60-year-old female, who was referred to the Bielanski Hospital with signs and symptoms of acute appendicitis. Microscopic examination of the appendix showed features of acute appendicitis, however scattered groups of cells with clear cytoplasm as well as strands of single cells with no evidence of atypia were seen. The patient underwent a right hemicolectomy due to the diagnosis of GCC.

Overexpression of 5-lipoxygenase in sporadic colonic adenomas and a possible new aspect of colon carcinogenesis.

PURPOSE: We aimed to study the intracellular expression of 5-lipoxygenase (5-LOX), the primary competitor with cyclooxygenase-2 in arachidonic acid metabolism, as inflammatory enzymes may be involved in blocking apoptosis and promoting cancer growth by changing arachidonic acid metabolism within cells. Our purpose was to investigate the possible connection between 5-LOX expression and colon carcinogenesis by characterizing 5-LOX expression in histologically different colonic adenomas, determining the relationship between high expression of 5-LOX and various conventional clinicopathological features of adenomas, and finally characterizing the histological localization of cells with 5-LOX overexpression. METHODS: A total of 111 patients were examined and 120 histologically different colonic adenomas analyzed (including four cases of intramucosal adenocarcinoma in a polyp). Immunohistochemical staining with polyclonal anti-5-LOX antibodies was performed. RESULTS: There was a significant correlation between high 5-LOX expression and patient age, increased polyp size, high grade of intraepithelial neoplasia, villous and tubulovillous adenoma, and histological epithelial localization. CONCLUSIONS: We observed a strong positive correlation between 5-LOX overexpression and the appearance of typical high-risk factors for malignant transformation in adenomatous polyps. The results support the role of 5-LOX in early stages of colon carcinogenesis.

Genetic Variants of the IL2 Gene Related to Risk and Survival in Patients With Colorectal Cancer.

BACKGROUND: Interleukin 2 (IL2) is a significant factor activating T-cell-mediated immune response by stimulation of natural killer cells, T-cells and in development of regulatory T (Treg) cells. Recent studies have that IL2 participates in cancer development by modifying the local immune response. Based on the suggested role of the single nucleotide polymorphisms (SNPs) rs2069762, rs6822844 and rs11938795 of IL2 in the pathogenesis of certain diseases, the relationship of these SNPs with clinicopathological variables and their possible implication for prognosis and disease outcome were evaluated in a cohort of Swedish patients with colorectal cancer (CRC). MATERIALS AND METHODS: TaqMan SNP genotype assays based on polymerase chain reaction were used for analysis of the IL2 SNPs in 467 patients with CRC and 467 healthy controls. Expression analysis of IL2 in plasma and CRC tissue was also performed. RESULTS: The allelic variants T in rs11938795 and G in rs6822844 were significantly associated with a higher risk of CRC. Kaplan-Meier analysis showed that cancer-specific survival was worse for individuals with C allele for rs2069762 with stage II CRC and with T allele for rs6822844 with stage III CRC. CONCLUSION: SNPs rs2069762, rs6822844 and rs11938795 of the IL2 gene may be helpful as prognostic biomarkers in the follow-up and management of the patients.

Protein Expression and Genetic Variation of IL32 and Association with Colorectal Cancer in Swedish Patients.

BACKGROUND: Interleukin 32 (IL32) is an intracellular pluripotent cytokine produced by epithelial cells, monocytes, T-lymphocytes and natural killer cells and seems to be involved in the pathogenesis of cancer and inflammatory diseases. Our purpose was to assess the role of protein expression and genetic polymorphisms of IL32 in colorectal cancer (CRC) susceptibility. MATERIALS AND METHODS: To gain insight into clinical significance of IL32 in Swedish patients with CRC, using enzyme-linked immunosorbent assay, we determined whether IL32 protein level is altered in CRC tissue (n=75) compared with paired normal tissue and in plasma from patients with CRC (n=94) compared with controls (n=81). The expression of IL32 protein was confirmed by immunohistochemistry (n=73). We used Luminex technology to investigate protein levels of the cytokines IL6, tumor necrosis factor-α (TNFα) and vascular endothelial growth factor (VEGF) to relate these to IL32 levels in CRC tissue. Three single nucleotide polymorphisms (SNPs) (rs28372698, rs12934561, rs4786370) of the IL32 gene have been proposed as modifiers for different diseases. The present study evaluated the susceptibility of patients possessing these SNPs to CRC. Using TaqMan SNP genotyping assays, these SNPs were screened in Swedish patients with CRC (n=465) and healthy controls (n=331). RESULTS: We found no significant differences in the genotypic frequencies between the patients and healthy controls and no relation to survival for any of the SNPs. However, the SNP rs12934561 was statisticalLY significant associated with older patients. IL32 protein was up-regulated in CRC tissue and related to IL6, TNFα, and VEGF, and seems to be modulated by SNP rs28372698. The IL32 protein level in CRC tissue also reflects both disseminated disease and location. CONCLUSION: Our results suggest that altered IL32 protein concentrations in CRC tissue and genotypic variants of IL32 are related to disseminated CRC.

Butyrate inhibits cytokine-induced VCAM-1 and ICAM-1 expression in cultured endothelial cells: the role of NF-kappaB and PPARalpha.

Adhesion and migration of leukocytes into the surrounding tissues is a crucial step in inflammation, immunity, and atherogenesis. Expression of cell adhesion molecules by endothelial cells plays a leading role in this process. Butyrate, a natural short-chain fatty acid produced by bacterial fermentation of dietary fiber, has been attributed with anti-inflammatory activity in inflammatory bowel disease. Butyrate in vitro is active in colonocytes and several other cell types. We have studied the effect of butyrate on expression of endothelial leukocyte adhesion molecules by cytokine-stimulated human umbilical vein endothelial cells (HUVEC). Pretreatment of HUVEC with butyrate-inhibited tumor necrosis factor-alpha (TNFalpha)-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) in a time and concentration-dependent manner. Butyrate at 10 mM/L inhibited interleukin-1 (IL-1)-stimulated VCAM-1 and ICAM-1 expression. The effect of butyrate on cytokine-stimulated VCAM-1 expression was more pronounced than in the case of ICAM-1. Butyrate decreased TNFalpha-induced expression of mRNA for VCAM-1 and ICAM-1. Suppressed expression of VCAM-1 and ICAM-1 was associated with reduced adherence of monocytes and lymphocytes to cytokine-stimulated HUVEC. Butyrate inhibited TNFalpha-induced activation of nuclear factor-kappaB (NF-kappaB) in HUVEC. Finally, butyrate enhanced peroxisome proliferator-activated receptor-alpha (PPARalpha) expression in HUVEC. These results demonstrate that butyrate may have anti-inflammatory properties not only in colonocytes but also in endothelial cells. The anti-inflammatory and (perhaps) antiatherogenic properties of butyrate may partly be attributed to an effect on activation of NF-kappaB and PPARalpha and to the associated expression of VCAM-1 and ICAM-1. The present findings support further investigations on the therapeutic benefits of butyrate in several pathological events involving leukocyte recruitment.

Angiogenesis as determined by computerised image analysis and the risk of early relapse in women with invasive ductal breast carcinoma.

The purpose of this study was to define the value of angiogenesis as a prognostic factor indicating early relapse. We assessed the relationship between parameters of angiogenesis (microvessel count--MVC, microvessel area--MVA and microvessel perimeter--MVP) and relapse-free survival at 50 months in 226 women with invasive ductal breast carcinoma. Anti CD31 antibody was used as a marker of endothelial cells. Microvessel density was measured according to Weidner et al. using a computerised image analysis. The mean parameters of angiogenesis were significantly higher in women with relapse than in those without recurrence within 50 months after surgery. In node negative patients relapse did not occur if MVC was below 38.7. In node-negative subgroup with grade II carcinomas parameters of angiogenesis in the primary tumour differed significantly depending on the presence or absence of relapse. Univariate and multivariate analysis showed the prognostic value of angiogenesis parameters in all study groups with respect to 50-month relapse-free survival. In node negative subgroup only 62.5% of women with tumors with high MVC and as much as 94.9% with low MVC survived 50 months without recurrence. In the Cox analysis of node-negative subgroup only MVC, MVP and MVA were the independent prognostic factors. In women with node-negative disease the evaluation of angiogenesis can identify a subgroup of patients with high risk of relapse, hence it may help in decisions concerning adjuvant therapy. Computerised image analysis is a good and objective technique for evaluating the intensity of angiogenesis in breast cancer.

[Pathomorphology of the thyroid gland after treatment of laryngeal cancer]. / Patomorfologia gruczolu tarczowego po leczeniu raka krtani.

The aim of the report was the explanation of the pathogenesis of thyroid gland dysfunction after laryngeal cancer treatment. Assessment of histopathological specimens from thyroid gland was done. They were taken from the following patients: a) irradiated primary with the radical dose (n = 5), b) after combined therapy (n = 2) and c) at the autopsy from the persons aged between 30-80, without thyroid gland disease history (n = 30). It was found that the thyroid gland underwent degenerative changes after external irradiation or combined therapy, which became more intense with the passage of time. They consist among other things in diminishing of the follicle lining cells with the obliteration of the follicle structure of thyroid, damage to the blood vessel walls, fibrotic tissue proliferation with the following gland atrophy. In the histological specimens of the thyroid gland taken at the autopsy distinct obliteration of the follicle structure with the atrophy of follicle and intensified fibrotic process after 80 years of age was seen. Results of the investigations suggest that the main pathogenic factor in hypotyhyreosis after radiotherapy or combined therapy are the degenerative changes in the thyroid gland and their overlapping with circulatory disorders after surgery. Morphological changes in thyroid gland following aging increase the risk of hypotyhyreosis.

[Histomorphology of the pharyngoesophageal sphincter as prognostic factor of developing esophageal speech]. / Histomorfologia zwieracza gardlowo-przelykowego jako czynnik prognostyczny w opanowaniu mowy przelykowej.

Histomorphologic evaluation of the pharyngoesophageal sphincter (pes) in the decreased persons aged 11-82 was done. These persons, in the lifetime, never suffered from: a) neurologic diseases (among others-myasthenia, progressive muscle atrophy), b) neoplasm of the esophagus, c) dysphagia. The aim of the report was the explanation whether the degenerative changes in pes, seen in the course of ageing, should be included into the risk factors of the high pressure occuring in its area after total laryngectomy. The analysis of the histopathological specimens revealed that after 40 years of age connective tissue in the pes is spreading and the number of muscular fibers is decreasing. Till 60 years of age the degenerative process in pes is very differentiated. Some histopathological specimens, in persons of this age section, didn't differ much from those seen in young cases. In the following decades o life degenerative process intensifies successively. In the histopathological specimens intensive proliferation of the fibrotic and fat tissue was found and considerable decrease of muscular fiber number. The investigations on risk factors of high pressure in the area of pes (results made know in paper given for print) revealed that in elder patients after total laryngectomy, its values are higher than in young ones. In patients till 55 years of age, in 72.29% (n = 26/36) of examined cases, the pressure in the pes area didn't exceed 3.99 kPa (30 mmHg). In the age of 55 years and above such a pressure was observed only 39.1% (n = 18/46) of examined. Degenerative changes in pes, depending on age, can be in part of patients (particularly in elder ones) one of the risk factors of the high pressure in the pes area, which should be taken in account in prognosis of esophageal speech mastering by the patient.

[Factors influencing the hormonal function in patients after the treatment of larynx cancer]. / Czynniki wplywajace na utrzymanie sie prawidlowej funkcji hormonalnej tarczycy u pacjentów po leczeniu raka krtani.

It has been revealed that the hypothyreosis (subclinical as a rule) can be found after every method applied in treatment of the larynx cancer. Correlation of data obtained with the time function allowed to specify survival probability of patients in euthyreosis after therapy termination. Among the factors supposed to be involved in keeping patient's normal thyroid gland function the following have been taken into account: sex, age, stage of the neoclassic process, scope of the surgical intervention on the larynx and lymph nodes of the neck, thyroid gland surgery and dose of irradiation given in Gy/T at the time of radiotherapy. Substantial impact on hypothyreosis was attributed to: method of laryngeal cancer, treatment, the range of its structures removal and surgical intervention on thyroid gland (excision of the thyroid lobe or its translocation for larynx reconstruction). It was found that the probability of survival in euthyreosis in patients treated by surgery and by combined method was the least after laryngopharyngectomy. In 3 years follow up period after such a therapy it amounted to 75% for surgical method and 48% for combined one. It was evident that the dysfunction of the thyroid gland resulted mostly from combined method of laryngeal cancer therapy (even without surgical intervention on thyroid glad). The probability of survival in euthyreosis in those patients was the least of all and amounted to 78.7% after 1 year of therapy termination and 42.9% after 6. In patients treated with combined method and intervention on thyroid gland, the survival probability in euthyreosis was 25% after excision thyroid lobe and 20% after its translocation for larynx reconstruction. After exclusive surgical therapy the probability amounted to 96% and after radiotherapy 88.6%. Prolongation of the follow up after radiotherapy (over 1 year) didn't increase the number of patients with hypothyreosis. The necessity of the evaluation of the thyroid gland hormonal function in every one patient has been stressed. This should be done before treatment and 1, 6, and 12 months after the termination of the therapy, and then once a year.

Expression of cyclooxygenase-2 in colonic polyps.

INTRODUCTION: Limited data is available regarding the relationships between cyclooxygenase-2 (COX-2) and colorectal cancer formation. OBJECTIVES: The aim of the study was to investigate cyclooxygenase-2 (COX-2) expression in histologically diverse colonic polyps, to determine the association between the expression of this enzyme and selected patho logical and clinical characteristics of polyps, and to establish the location of cells with high COX-2 expression within the polyp. PATIENTS AND METHODS: We examined 212 colonic polyps from 175 patients. Immunohistochemical staining with monoclonal anti-COX-2 antibodies was performed. RESULTS: Statistically significant differences associated with high COX-2 expression were found: in adenomas vs. other polyps (P <0.001), in adenomas with high-grade dysplasia (P <0.000 001), and in polyps of the cecum (P <0.02). Statistically significant differences in COX-2 were also associated with polyp size (P <0.000 001). Cells with high COX-2 expression were usually located in the epithelial layer (P = 0.01). No significant associations were found between high COX-2 expression and the age and sex of patients or the total number of polyps. CONCLUSIONS: We demonstrated that high COX-2 expression is associated with typical risk factors for malignant transformation of colonic polyps. The results suggest the possible role of COX-2 in the early stages of colon carcinogenesis.