Kudo's pit pattern classification for in vivo optical diagnosis and discrimination of advanced colorectal polyps.

OBJECTIVE: Colonoscopy is currently the basic diagnostic tool for the large intestine. The size of lesions assessed during the investigation is one criterion for assessing the risk of polyps transforming into colorectal cancer. The techno-logical development of endoscopes and the possibility of direct assessment of lesion's surface during the endoscopic examination and to use appropriate treatment. The aim of this study is to analyze the consistency between the histopathological assessment of high-risk lesions in colonoscopy and the determination according to Kudo's pit pattern classification. PATIENTS AND METHODS: The analysis included the results of colonoscopies performed over a 2-year period, in which polyps were diagnosed endoscopically and either polypectomies were performed, or sections were taken from these polyps and a pit pattern analysis was done according to Kudo's classification. RESULTS: A total of 1038 patients (age, 67.2 ± 12.7 years) were enrolled in the study. Of the 1981 samples taken in total, polyps larger than 1 cm were found in 96 cases, laterally spreading tumors (LSTs) were found in 48 cases, and macroscopic infiltration or tumors were found in 110 cases. The results of the histopathological examination were obtained in 248 cases. A value of 4 or higher in the Kudo classification turned out to be the best parameter to differentiate malignant lesions from benign ones for lesions larger than 1 cm and laterally spreading tumors, with a sensitivity of 91.2% and a specificity of 70.4%. CONCLUSIONS: The assessment of polyps according to Kudo's classification is a useful tool for assessing the malignancy of lesions as part of a routine colonoscopy.

Ketoprofen and tramadol pharmacokinetics in patients with chronic pancreatitis.

OBJECTIVE: Chronic pancreatitis (CP) is a disease leading to irreversible pancreas dysfunction. One of the main symptoms is pain. Many patients require pharmacological therapy which should be started with paracetamol or, in selected groups of patients, ketoprofen. If the effect of ketoprofen is irrelevant, patients receive tramadol. The aim of this study is the evaluation of ketoprofen and tramadol pharmacokinetics (PK) in CP patients. PATIENTS AND METHODS: 36 patients were divided into two groups: I - receiving ketoprofen (n=18; mean [SD] age, 48.61 [13.32] years; weight, 73.28 [20.48] kg), II - receiving tramadol (n=18; mean [SD] age, 46.78 [10.28] years; weight, 74.22 [14.04] kg, and BMI (Body Mass Index), 24.61 [4.51] kg/m2). The plasma concentrations of ketoprofen and tramadol with its active metabolite M1 (0-desmethyltramadol) were measured with the validated high-performance liquid chromatography method. RESULTS: The main PK parameters for ketoprofen were as follows: Cmax (maximum plasma concentration), 3.41 [2.32] mg/L; AUC0-inf (area under the plasma concentration-time curve from time zero to infinity), 10.45 [5.57] mg⋅h/L; tmax (time to first occurrence of Cmax), 1.94 [1.25] h; Cl (clearance), 0.199 [0.165] L/kg·h, and Vd/kg (volume of distribution per kilogram of body weight), 0.71 [0.58] L/kg. The main PK parameters for TRM and M1 were as follows: Cmax, 226.4 [80.5] and 55.6 [23] ng/mL; AUC0-inf, 1903.3 [874.8] and 790.4 [512.4] ng⋅h/mL; tmax, 1.78 [0.73] and 2.67 [1.19] h, respectively. CONCLUSIONS: Chronic pancreatitis led to a decrease in the total amount of absorbed ketoprofen. Consequently, the analgesic effect of the drug may be weaker. Cmax of tramadol for most CP patients was within the therapeutic range associated with its analgesic activity. M1/TRM ratios for Cmax and AUC were unchanged.

Differential antitumor effects of vitamin D analogues on colorectal carcinoma in culture.

Colorectal cancer (CRC) is an emerging global problem with the rapid increase in its incidence being associated with an unhealthy lifestyle. Epidemiological studies have shown that decreased levels of vitamin D3 significantly increases the risk of CRC. Furthermore, negative effects of vitamin D3 deficiency can be compensated by appropriate supplementation. Vitamin D3 was shown to inhibit growth and induce differentiation of cancer cells, however, excessive vitamin D3 intake leads to hypercalcemia. Thus, development of efficient vitamin D3 analogues with limited impact on calcium homeostasis is an important scientific and clinically relevant task. The aims of the present study were to compare the antiproliferative potential of classic vitamin D3 metabolites (1α,25(OH)2D3 and 25(OH)D3) with selected low calcemic analogues (calcipotriol and 20(OH)D3) on CRC cell lines and to investigate the expression of vitamin D-related genes in CRC cell lines and clinical samples. Vitamin D3 analogues exerted anti-proliferative effects on all CRC cell lines tested. Calcipotriol proved to be as potent as 1α,25(OH)2D3 and had more efficacy than 20-hydroxyvitamin D3. In addition, the analogs tested effectively inhibited the formation of colonies in Matrigel. The expression of genes involved in 1α,25(OH)2D3 signaling and metabolism varied in cell lines analysed, which explains in part their different sensitivities to the various analogues. In CRC biopsies, there was decreased VDR expression in tumor samples in comparison to the surgical margin and healthy colon samples (p<0.01). The present study indicates that vitamin D3 analogues which have low calcemic activity, such as calcipotriol or 20(OH)D3, are very promising candidates for CRC therapy. Moreover, expression profiling of vitamin D-related genes is likely to be a powerful tool in the planning of anticancer therapy. Decreased levels of VDR and increased CYP24A1 expression in clinical samples underline the importance of deregulation of vitamin D pathways in the development of CRC.

Endoscopic drainage/debridement of walled-off pancreatic necrosis--single center experience of 112 cases.

BACKGROUND: Endoscopic drainage of the pancreatic pseudocysts has been accepted as a valid alternative to surgical and percutaneous drainage. Endoscopic treatment of the symptomatic walled-off necrosis was not, however, univocally accepted by all authors. THE AIM: The aim of this study was to assessed the effectiveness and safety of the endoscopic drainage of walled-off necrosis. METHODS AND MATERIAL: Between 2001 and 2011 one hundred and twelve patients with symptomatic walled-off necrosis were treated in the Department of Gastroenterology and Hepatology of the Medical University of Gdansk, using endoscopic drainage. The drainage system was set up by introducing endoprostheses and drains through gastric and duodenal fistulas, transpapillary, and additionally--in cases when the necrosis was spreading outside of the lesser sac--percutaneously. The results and complications of the endoscopic treatment were assessed retrospectively. RESULTS: Initial success was achieved in 104/112 (92.9%) patients. Long term success was achieved in 94/112 (83.9%) patients in intention to treat analysis and 94/102 (90.4%) patients in per protocol analysis. Recurrence of pancreatic fluid collection was observed in 19/97(19.6%) patients. Procedure-related complications were observed in 29/112 patients (25.9%). Most of them were treated conservatively. Procedure-related mortality was 1.8%. CONCLUSIONS: In a large group of selected patients with symptomatic walled-off necrosis, endoscopic drainage enables high success rate with acceptable complication rate and low procedure-related mortality.

Influence of receptor activator of nuclear factor kappa B ligand, osteoprotegerin and interleukin-33 on bone metabolism in patients with long-standing ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic disease with periods of remission and recurrences. Dysfunction of the local immune response leads to chronic inflammation within the large intestine which triggers morphological changes in the intestinal wall as well as induces the synthesis of numerous factors that have an adverse impact on the bone metabolism. The aim of the study was to determine the expression of RANKL, OPG and IL-33 in mucosal biopsies of UC patients with long disease duration as well as serum level of these cytokines in the context of bone density and bone metabolism. MATERIALS AND METHODS: The UC group consisted of 56 patients with average disease duration of 16y. The control group comprised 37 healthy individuals. Local expression of cytokines was assessed in the biopsies of colonic mucosa by the real-time PCR and immunohistochemistry (IHC), and their serum concentration was measured by ELISA. RESULTS: The increased bone resorption observed in patients with UC was reflected by low bone density and high serum level of C-terminal telopeptide (CTX). Mucosal RANKL expression and serum concentration were similar in UC group and healthy subjects, however, UC patients had higher local expression of OPG and serum OPG concentration. Increased IL-33 gene expression was observed only in UC at the mRNA level. We propose that bone resorption in UC patients despite OPG up-regulation could be caused by IL-33-induced mucosal synthesis of a potent proinflammatory cytokine, such as TNF-α, known as a possible inducer of osteoclastogenesis in the way independent of RANKL.

Overexpression of the fragile histidine triad (FHIT) gene in inflammatory bowel disease.

OBJECTIVE: FHIT gene encodes human diadenosine triphosphate hydrolase involved in the regulation of cell cycle and nucleotide metabolism and is a candidate tumor suppressor gene. AIM: To investigate expression of FHIT gene at the mRNA and protein levels in sporadic inflammatory bowel disease (IBD). MATERIALS AND METHODS: FHIT mRNA was quantified by the validated real-time PCR (QPCR) and FHIT protein was detected by immunohistochemistry (IHC) in mucosal biopsies of 139 ulcerative colitis (UC), 19 Crohn's disease (CD) and 37 control patients. RESULTS: Significant FHIT gene overexpression was found in 78% of active UC but not in CD. IHC showed comparable results to QPCR. CONCLUSION: The local up-regulation of FHIT gene and protein expression in active UC may represent an adequate response against inflammatory challenge of epithelial cell homeostasis and protect against DNA damage and cell cycle disturbances.

Fragile histidine triad (FHIT) gene is overexpressed in colorectal cancer.

OBJECTIVE: FHIT gene, mapped at FRA3B site, encodes human diadenosine triphosphate hydrolase involved in the regulation of cell cycle and nucleotide metabolism. Decreased FHIT gene expression was previously observed in various types of human cancer, however, quantification of FHIT mRNA was seldom performed. AIM: To investigate loss of heterozygosity (LOH) at FRA3B, expression of FHIT gene at the mRNA and protein levels in sporadic colorectal carcinoma (CRC) and benign colon adenoma. MATERIALS AND METHODS: FHIT mRNA was quantified by the validated realtime PCR (QPCR) in tumor samples of 84 CRC patients and mucosal biopsies of 15 adenomas, in comparison to 37 control patients, whereas subgroup of 57 CRC, 10 adenoma and 10 control cases were selected for immunohistochemical (IHC) detection of the native FHIT protein and LOH determination at FRA3B. RESULTS: Higher level of FHIT mRNA was found in 86% of CRC (P<0.001) and 60% of adenomas (P=0.016). IHC showed comparable results to QPCR (P=0.003), revealing the strongest presence of FHIT protein in Dukes' C/D stages (P<0.001) and N1/N2 lymph nodes metastasis in CRC (P=0.04). FHIT gene expression and Dukes' and G staging were positively correlated in CRC as analyzed by QPCR and IHC. Deletion analysis of the fragile FRA3B site revealed the highest LOH frequency at D3S1234 in 32.5% of CRC informative cases, however, LOH did not correspond to QPCR, IHC or clinical-pathological variables. CONCLUSION: Our data suggest that reduction or absence of the FHIT gene expression is not a prerequisite for colorectal cancer development and progression.

Decreased Toll-like receptor-5 (TLR-5) expression in the mucosa of ulcerative colitis patients.

OBJECTIVE: Although there is a convincing evidence supporting an important role for microorganisms in the pathogenesis of Inflammatory Bowel Disease (IBD) which comprises ulcerative colitis (UC) and Crohn's disease (CD), the specific mechanisms involved remain unclear. Toll-like receptors (TLR) recognize various molecules of microbiota including flagellin, the principal protein of motile comensal and pathogenic bacteria implicated in the pathogenesis of IBD. AIM: To investigate the expression of the TLR-5 receptors at the mRNA and protein levels in the mucosa of UC patients. MATERIALS AND METHODS: TLR-5 mRNA was quantified by the validated real-time PCR (QPCR) in mucosal biopsies of 99 UC patients and 34 control patients and TLR-5 protein was detected by immunohistochemistry (IHC) in 57 UC and 10 control patients. RESULTS: Significantly decreased TLR-5 gene expression at mRNA and protein level was found in the mucosa of patients with moderate and severe disease activity as compared to patients with low UC activity and control. TLR-5 immunoreactivity was found in the mucosa of UC patients and normal controls in the cytoplasm of enterocytes and at their basolateral domain. However, the intensity of the IHC reaction in specimens from UC patients was substantially lower than in control samples. CONCLUSION: The decreased expression of TLR-5 gene and protein in the mucosa of UC patients suggests that down-regulation of TLR-5 is probably caused by the increased number of ligand molecules in the proximity of epithelial cells in the inflamed tissue.

[Occurrence of gastrointestinal diseases among workers in a ceramics factory]. / Wystepowanie chorób przewodu pokarmowego wsród pracowników zatrudnionych w zakladzie ceramicznym.

A group of doctors from the Medical Academy of Gdansk carried out epidemiological studies, including internal diseases, in workers of the "Lubiana" china ceramics factory. The main purpose of the study was to improve prevention and health care of this occupational group. The paper presents clinical and epidemiological problems pertaining to the gastrointestinal diseases in the factory staff members. They were subject to physical and many other examinations taken at the Medical Academy mostly in the Clinic of Gastroenterology. The study revealed that gastrointestinal diseases made one third of all ailments in this group of workers. Stomach and duodenum ulcers proved to be the most common diseases among males while females suffered more from other gastrointestinal diseases. Among males the 36-50 age group and among females the 21-35 age group were mostly affected. Intensive smoking and irregular life-style contribute significantly to the increased incidence of gastrointestinal diseases.

[Diagnostic and therapeutic difficulties in staphylococcal sepsis]. / Trudnosci diagnostyczno-lecznicze posocznic gronkowcowych.

A case is described of a 38-year-old man treated for three years for diabetes mellitus admitted to an internal department for elucidation of the cause of protracted fever. Staphylococcal sepsis was diagnosed with pneumonia and retroperitoneal abscess. Surgical treatment was given and targeted antibiotic-therapy was administered. The patient was discharged from the hospital after 38 days as cured. An observation of 18 months failed to show the recurrence of the infection.

Tetra-t-butoxydisiloxane-1,3-diyl, a new type of bifunctional silyl protective group.

Tetra-t-butoxydisiloxane-1,3-diyl (TBDSi) group is introduced into nucleoside chemistry as an analogue of tetraisopropyldisiloxane-1,3-diyl (TIPDSi) and an example of a new type of bifunctional silyl protective group. Its introduction and properties of derivatives of ribonucleosides are presented.