The experience with colorectal cancer screening in the Czech Republic: the detection at earlier stages and improved clinical outcomes.

OBJECTIVES: Colorectal cancer (CRC) remains a major health burden. Although screening is recommended and considered beneficial, further data on its positive effects are needed for worldwide implementation. STUDY DESIGN: The aim of our national multicentre prospective observational study was to reveal and document clinicopathological differences in CRC diagnosed by screening and presented by disease symptoms as well as assess the efficiency of the screening programme in the Czech Republic. METHODS: Between March 2013 and September 2015, a total of 265 patients were enrolled in 12 gastroenterology centres across the Czech Republic. Patients were divided into screening and symptomatic groups and compared for pathology status and clinical characteristics. Screening was defined as a primary screening colonoscopy or a colonoscopy after a positive faecal occult blood test in an average-risk population. RESULTS: The distribution of CRC stages was significantly (statistically and clinically) favourable in the screening group (predominance of stages 0, I and II) compared with the non-screening group (P < 0.001). The presence of distant and local metastases was significantly less frequent in the screening group than in the symptomatic group (P < 0.001). Patients in the screening group had a higher probability of radical surgery (R0) than those diagnosed based on symptoms (P < 0.001). Systemic palliative treatment was indicated in two patients in the screening group compared with 23 patients in the non-screening group (P = 0.018). CONCLUSION: CRC diagnosed by screening disclosed less advanced clinicopathological characteristics and results in patients with a higher probability of radical surgery (R0) than diagnoses established based on symptoms, with subsequent management differing accordingly between both groups. These results advocate the implementation of a suitable worldwide screening programme.

Fixation of biomaterial to metallic stent and fixation of stents after circular endoscopic dissection in the esophagus on an animal model.

INTRODUCTION: Complete circular endoscopic (submucosal) resection (CER) performed using the endoscopic submucosal dissection (ESD) technique is burdened with a high incidence of post-operative strictures in the esophagus. The most effective method of preventing them is not known so far; one of the possible methods is to prevent these strictures directly at the site of their formation by covering the defect with a stent. The aim of the study was to find a way to fix a selected biomaterial to a stent, and subsequently, to fix the stent at the CER site to prevent esophageal strictures in an animal model. METHOD: Miniature piglets from the Czech Academy of Sciences breeding unit in Libechov (N=10) were used. Endoscopy was performed using a single-channel endoscope. First, we made two circular mucosal cuts spaced 5 cm apart in the middle esophagus and we performed the CER between them using the endoscopic submucosal dissection technique. After that, we covered the defect with a stent coated with biomaterial (Xe-Derma®) while we tried to prevent stent migration into the stomach. For stent fixation, we tested endo-clips (N=3), the Apollo endoscopic system (N=1) and the suspension technique using two polyamide threads (N=6) anchored in the nasal septum. We performed a control endoscopy, stent removal and subsequent autopsy after 12 weeks. RESULTS: All procedures were completed successfully without serious complications or deaths. Although stents covered with Xe-Derma® were applied to the entire resection area, one case of mediastinitis and one paraesophageal abscess were found during autopsy, most likely due to microperforations caused during the procedure. Histological analysis showed that after contact with the biomaterial, re-epithelisation took place within one week of application to the resection area. Stent migration occurred in each case when the stent was attached to the esophageal wall by endo-clips or with the endoscopic suture system (Apollo). There was no stent dislocation in the cases where the stent was suspended by two polyamide threads. CONCLUSION: We developed a technique of fixing biomaterial to the surface of metallic stents which we used to prevent the formation of esophageal strictures after CER. Distal suspension fixation of the stent with a polyamide thread proved to be the most effective, while fixations by endo-clips or with the endoscopic suture system were ineffective.Key words: benign esophageal strictures circular endoscopic resection endoscopic submucosal dissection complication prevention.

[Molecular Pathogenesis of Colorectal Cancer]. / Molekulární genetika kolorektálního karcinomu.

BACKGROUND: Colorectal cancer (CRC) remains a major health burden with an incidence of 1.3 million new cases worldwide and a mortality of almost 8.5%. It is the 2nd most common cancer in women (1st breast carcinoma) and 3rd most common in men (1st lung carcinoma, 2nd prostate carcinoma). CRC alongside breast, lung, prostate and stomach cancer is in the top five most common cancers in men and women worldwide. There are still more than 50% of CRC patients diagnosed with advanced disease (stage III and IV) in the Czech Republic. Genetically, CRC is a very heterogeneous disease with many factors playing key roles in pathogenesis. There are two types of CRC, hereditary with an incidence of between 5% and 10% with APC (FAP, aFAP) or MMR (HNPCC) genes affected, and sporadic colorectal cancer with an incidence of 90-95% with a lot of mutations in variable genes that accumulate during pathogenesis (APC, KRAS, MMR, microRNA, CIMP etc.). Knowledge of the molecular pathogenesis of CRC (hereditary, sporadic) is crucial for treatment, assessment of risk, prognosis, and patient follow-up. CONCLUSION: This article summarizes the molecular pathogenesis of sporadic and hereditary CRC.

'Obesity paradox' misunderstands the biology of optimal weight throughout the life cycle.

The 'obesity paradox' refers to observations that run counter to the thesis that normal weight (BMI 18.5-24.9 g/m(2)) provides the lowest mortality and higher weight is associated with greater mortality. We argue that the weight of lowest mortality is influenced by aging and chronic disease, with mortality advantage extending into the overweight and even class I obese ranges under some circumstances. A focus on quality nutrition, physical activity, fitness, and maintaining function in these weight ranges may be preferable to a focus on intentional weight loss, which has uncertain effects. The 'obesity paradox' is no 'paradox' if one defines and interprets 'ideal' weight appropriately.

Sex chromosome pairing and extensive NOR polymorphism in Wadicosa fidelis (Araneae: Lycosidae).

In terms of cytogenetics, entelegyne araneomorphs are the best studied clade of spiders. The typical karyotype of entelegyne males consists of acrocentric chromosomes, including 2 non-homologous X chromosomes. The present study is focused on the karyotype, nucleolus organising regions (NORs) and sex chromosome behaviour during meiosis of the entelegyne Wadicosa fidelis (Lycosidae). Preparations stained by Giemsa were used to study karyotype and meiosis. NORs were visualised by silver staining and fluorescence in situ hybridisation with 18S rDNA probe. The male karyotype consists of 28 acrocentric elements, including 2 X chromosomes. In contrast to the majority of other spiders, the male sex chromosomes pair during the major part of meiosis. Following an initial period of parallel pairing, the attachment of male sex chromosomes is restricted to centromeric areas and continues until metaphase II. Our study revealed an enormous number of NORs in the population from Galilee and indicates a considerable variability of NOR numbers in this population. The distal regions of 9 or 10 autosomal pairs contain NORs. The obtained data indicate the rapid spread of NORs in the karyotype of W. fidelis, which was presumably caused by ectopic recombinations and subsequent hybridisations of individuals with different NOR genotypes that produced heterozygotes.

The first cytogenetic characterization of atemnids: pseudoscorpions with the highest chromosome numbers (Arachnida: Pseudoscorpiones).

The karyotypes of pseudoscorpions of the family Atemnidae (Arachnida: Pseudoscorpiones) were studied for the first time. Karyotype data for 7 species have been obtained. The diploid chromosome numbers of most species considerably exceed the numbers reported in pseudoscorpions so far, with males ranging between 65 and 143. In spite of this, the sex chromosome system of atemnids is characterized by the same features that are found in the majority of other pseudoscorpions with an X0 system; the X chromosome is metacentric and is the largest chromosome or one of the largest chromosomes of the karyotype. Male meiotic cells of Atemnus politus contain 1 or 2 autosome multivalents; most specimens had 2 multivalents. The multivalents were composed of 4, 6, 8 or 10 chromosomes. Multivalent number and structure was consistent within each of the studied individuals. The same number of chromosomes in all of the males examined suggests that multivalents are generated by reciprocal translocations. The high diversity of multivalents suggests considerable range of translocation heterozygosity in the studied population.

Microdialysis in early detection of temporary pancreatic ischemia in a porcine model.

BACKGROUND: Ischemic injury to the pancreas occurs in various clinical conditions. A method for online monitoring of pathophysiological events in pancreatic parenchyma is missing. AIMS: To assess the timing of microdialysis (MD) technique response on temporary changes in pancreatic perfusion, and to evaluate the relationship between MD data and systemic markers of anaerobic metabolism and inflammation. METHODS: In anaesthetized normoventilated pigs, MD probes were placed in right (control) and left (ischemic) pancreatic lobes, respectively. Following the clamping of the vessels, ischemia was verified by tissue oxygen tension (P(ti)O(2)) measurements. RESULTS: P(ti)O(2) decreased within 20 min after the clamping of the vessels, already returning to baseline levels at the first sampling point after the removal of the clamp. MD lactate levels increased, whereas pyruvate and glucose levels decreased at 20 min after the induction of ischemia. These trends continued until the end of ischemia and returned to baseline following reperfusion. Serum lactate, amylase and tumor necrosis factor-alpha levels decreased throughout the protocol time. CONCLUSION: MD data were in concordance with changes in P(ti)O(2), which is indicative of local anaerobic metabolism. MD allowed the detection of pathophysiological processes within the ischemic pancreas at a stage when no elevations of systemic markers of ischemia or inflammation were observed.

Insights into the meiotic behavior and evolution of multiple sex chromosome systems in spiders.

A characteristic feature of spider karyotypes is the predominance of unusual multiple X chromosomes. To elucidate the evolution of spider sex chromosomes, their meiotic behavior was analyzed in 2 major clades of opisthothele spiders, namely, the entelegyne araneomorphs and the mygalomorphs. Our data support the predominance of X(1)X(2)0 systems in entelegynes, while rare X(1)X(2)X(3)X(4)0 systems were revealed in the tuberculote mygalomorphs. The spider species studied exhibited a considerable diversity of achiasmate sex chromosome pairing in male meiosis. The end-to-end pairing of sex chromosomes found in mygalomorphs was gradually replaced by the parallel attachment of sex chromosomes in entelegynes. The observed association of male X univalents with a centrosome at the first meiotic division may ensure the univalents' segregation. Spider meiotic sex chromosomes also showed other unique traits, namely, association with a chromosome pair in males and inactivation in females. Analysis of these traits supports the hypothesis that the multiple X chromosomes of spiders originated by duplications. In contrast to the homogametic sex of other animals, the homologous sex chromosomes of spider females were already paired at premeiotic interphase and were inactivated until prophase I. Furthermore, the sex chromosome pairs exhibited an end-to-end association during these stages. We suggest that the specific behavior of the female sex chromosomes may have evolved to avoid the negative effects of duplicated X chromosomes on female meiosis. The chromosome ends that ensure the association of sex chromosome pairs during meiosis may contain information for discriminating between homologous and homeologous X chromosomes and thus act to promote homologous pairing. The meiotic behavior of 4 X chromosome pairs in mygalomorph females, namely, the formation of 2 associations, each composed of 2 pairs with similar structure, suggests that the mygalomorph X(1)X(2)X(3)X(4)0 system originated by the duplication of the X(1)X(2)0 system via nondisjunctions or polyploidization.

[750 satisfied patients? Stapled haemorrhoidopexy (Longo procedure) for the treatment of haemorrhoids and anal canal prolapse: a review of our 10-year experience]. / 750 spokojených pacientu? 10 let zkuseností a výsledku Longovy metody operace hemoroidu a análních prolapsu.

INTRODUCTION: Haemorrhoid disease in a common ailment, which constitues a serious clinical and social problems, especially in countries having a significant level of development. There have been a great number of articles published on the method of treatment for haemorrhoid disease and anal canal prolapse with circular stapler introduced to clinical practise by Longo in the year 1993. However, there are very few studies devoted to assessment of this procedure in the Czech medical literature. AIM: Summary our 10 year experience--to perform a retrospective evaluation of early and long-term results of surgical treatment with a Longo procedure. PATIENTS AND METHODS: We evaluated retrospectively 750 patients, submitted in our hospital to Longo procedure since January 2000 until December 2009, considering results and complications of this procedure. 435 (58%) were women and 315 (42%) men, aged from 17 to 83 (46.2 years old on overall). Mean follow up was 5.5 months (ranged from 3 months to 3.5 years). RESULTS: Complications occurred in 76 patients (10.1%). In 24 patients (3.2%) during the early post-operative period. Late complications developed in 52 patients (6.9%). 34 patients (4.5%) required reoperation. Duration of hospitalisation after the procedure ranged from 2 to 8 days, an overage of 3.2 days. CONCLUSION: Longo procedure in indicated cases--treatment of the 3rd and 4th stage of haemorrhoid disease and anal canal prolapse, is an advisable alternative to other surgical methods. Has satisfactory short and long-term effects, lower postoperative pains, shortening of the patient's hospital stay. Longo's method is safe and suitable for the haemorrhoid therapy, can be recommended in selective patients for a one-day surgery scheme.

[The role of echocardiography in cardiovascular diseases assessment during pregnancy]. / Význam echokardiografie v diagnostice kardiovaskulárních onemocnení u tehotných zen.

Maternal heart disease complicates at least 1% of pregnancies and is one of the most important causes of maternal death. Echocardiographic examination provides valuable information about the size and function of cardiac chambers, valve morphology and function, hemodynamic consequences of various cardiac pathologies. It is particularly important during pregnancy when the complaints and physical signs may be misleading. Echocardiography is well suited to rapid diagnosis in pregnant women with known or suspected cardiac disorders. This review article deals with the contribution of echocardiography to precise diagnosis and management of cardiovascular diseases in pregnancy.

[Stapled hemorrhoidopexy (Long method)--procedure for prolapsing hemorrhoids (PPH)--eight-year experience with the method]. / Longova metoda operace hemoroidu a prolapsu sliznice anorekta (PPH)--zkusenosti 8 let.

Based on the author's long-term experience with stapled hemorrhoidopexy (procedure for prolapsing hemorrhoids-PPH), principal pros and cons of the procedure are presented in the article. Stapled hemorrhoidopexy is considered an option for radical and safe management of advanced hemorrhoid disorders.

[Recurrent peripheral arterial embolism from metastatic lung choriocarcinoma]. / Opakované embolizace do periferních tepen z plicní metastázy choriokarcinomu.

A case of patient with choriocarcinoma, most likely of ovarian origin, with lung metastasis is presented. The disease manifested by recurrent embolism into peripheral arteries. Publications on this topic are reviewed.

Does intra-abdominal adipose tissue in black men determine whether NIDDM is insulin-resistant or insulin-sensitive?

Insulin resistance in black Americans with non-insulin-dependent diabetes mellitus (NIDDM) is found in only 60% of those with a body mass index (BMI) of < 30 kg/m2, suggesting that NIDDM can occur independent of peripheral insulin resistance. When insulin resistance is present, it is not necessarily correlated with obesity. Numerous studies have shown that increased amounts of intra-abdominal adipose tissue are associated with various metabolic abnormalities. We therefore investigated whether the occurrence of insulin resistance in black NIDDM men could be explained by the pattern of body adipose tissue distribution rather than total adiposity. Twenty-two near-normoglycemic black men (fasting plasma glucose [mean +/- SD] = 104 +/- 10 mg/dl, HbA1c = 4.6 +/- 0.78%, age 48.9 +/- 9.2 years, and BMI 26.5 +/- 2.4 kg/m2) were studied. The euglycemic insulin clamp with 1 mU.kg-1.min-1 insulin infusion and D-[3-3H]glucose was used to measure insulin action. Whole-body computed tomography with 22 scans was used to determine body composition. Total body adipose tissue was 19.6 +/- 7.51, and the percentage of body fat was 27 +/- 7. Glucose disposal ranged from 2.5 to 8.1 mg.kg-1.min-1 (10 men were insulin-sensitive and 12 were insulin-resistant). There was a strong inverse correlation between glucose disposal and the proportion of total adipose tissue in the intra-abdominal region (r = -0.78, P < 0.001), while there was no correlation between glucose disposal and total muscle volume, BMI, total adipose tissue volume, or total subcutaneous adipose tissue volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic abnormalities in bulimia nervosa.

Resting metabolic rate was measured in a group of 22 women of normal body weight with bulimia nervosa and in 19 age-, sex-, and weight-matched control subjects. Mean resting metabolic rate of patients was significantly lower than that of controls (5162 +/- 928 vs 5636 +/- 449 kJ/24 h [1229 +/- 221 vs 1342 +/- 107 kcal/24 h]), as was mean fasting blood glucose level (4.0 +/- 0.6 vs 4.6 +/- 0.6 mmol/L). Mean basal thyrotropin level was significantly lower in patients than controls, but other thyroid indexes did not differ. There were no group differences in body fat mass, fat cell size, or lipoprotein lipase activity. These data suggest that there is a disturbance in energy regulation in bulimia nervosa. However, the origins and role of this disturbance in the pathophysiology of bulimia are unclear.

Angiotensin II receptors in human preadipocytes: role in cell cycle regulation.

The role of angiotensin II (AII) in human preadipocyte physiology has been investigated in primary cultures from human adipose tissue. Receptor binding studies indicated that human preadipocytes express a high affinity AII binding site of the AT1 subtype, as binding of 125I-labeled [Sar1,Ile8]AII was rapid, saturable, and specific. As AII has previously been demonstrated to affect the cell cycle in adrenal and cardiac cells, the effect of AII on regulation of cycle progression was examined in human preadipocytes. Stimulation of preadipocytes with AII resulted in G1 phase progression of the cell cycle, as determined by flow cytometric analysis. AII treatment was associated with induction of expression of the messenger RNA for the cell cycle regulatory protein cyclin D1 in a dose-dependent manner. Pretreatment of cells with subtype-selective AT receptor ligands before AII stimulation indicated that the cyclin response was mediated via the AT1 receptor. The identity of the cells as preadipocyte was verified by culture in a defined differentiation medium, observing both leptin message expression and triglyceride accumulation by flow cytometry. These findings indicate that AII has early, receptor-mediated effects on cell cycle progression in human preadipocytes that may contribute to differentiation to the adipocyte phenotype.

Autocrine regulation of human preadipocyte migration by plasminogen activator inhibitor-1.

One of the initial stages of adipogenesis is migration of preadipocytes of mesenchymal origin into cell clusters to form primitive fat organs. The serine protease inhibitor plasminogen activator inhibitor-1 (PAI-1) is synthesized and released from human adipose tissue ex vivo and regulates smooth muscle and endothelial cell migration in vitro, but its role in adipose tissue is not known. We investigated the role of PAI-1 in cultures of human preadipocytes from men and women of various ages and body mass indexes. Human preadipocytes expressed the messenger ribonucleic acid for PAI-1 and released significant quantities of PAI-1 protein into the medium. As PAI-1 regulates motility through the interaction of vitronectin with its receptor, the integrin alphaVbeta3, we identified this receptor in human preadipocytes. Flow cytometric analysis indicated that human preadipocytes express the vitronectin receptor alphaVbeta3 in a similar pattern as human umbilical vein endothelial cells. Functional studies indicated that active, but not latent, PAI-1 inhibited preadipocyte attachment to vitronectin with an IC(50) of 13.3 nmol/L, and preincubation of vitronectin-coated Transwells with active PAI-1 prevented preadipocyte migration. Vitronectin was identified in homogenates of the stromal-vascular fraction of human adipose tissue, but was absent from human adipocytes and cultured preadipocytes. These data indicate that human preadipocyte migration is regulated through the endogenous expression of PAI-1 and alphaVbeta3 integrin, a novel autocrine mechanism for potentially regulating cell cluster formation in adipogenesis.

Synthesis and secretion of plasminogen activator inhibitor-1 by human preadipocytes.

To further investigate the role of plasminogen activator inhibitor-1 (PAI-1) in adipose tissue physiology, the production and regulation of PAI-1 was determined in primary cultures of human preadipocytes. When expressed as production per cell and cultured under identical conditions, human preadipocytes from both visceral (omental) and sc depots of lean and obese individuals released significant, yet similar, amounts of PAI-1 protein into the conditioned medium. High steady-state PAI-1 messenger RNA (mRNA) concentrations were observed in visceral and sc preadipocytes, with the relative level of expression equivalent to beta-actin mRNA. Tumor necrosis factor alpha significantly decreased PAI-1 production in a concentration-dependent manner in both visceral and sc cultures, whereas transforming growth factor beta significantly elevated PAI-1 production, but only in sc preadipocytes from obese individuals. Addition of insulin had no effect on antigen levels in conditioned medium of preadipocyte cultures. Stimulation of the preadipocyte cultures with a defined medium resulted in differentiation to the adipocyte phenotype, as determined by flow cytometric analysis, verifying the cultures as human preadipocyte. These studies are the first to observe significant PAI-1 mRNA expression and protein production in primary cultures of a human adipose tissue cellular component, and they suggest that nascent adipocytes contribute significantly to the elevated plasma PAI-1 observed in obesity.

Liver pathology and the metabolic syndrome X in severe obesity.

The metabolic syndrome X, characterized by insulin resistance, dyslipidemia, hypertension, and a male, visceral distribution of adipose tissue, is associated with increased morbidity and mortality from several prevalent diseases, such as diabetes, cancers, myocardial infarction, and stroke. Because the liver has a central role in carbohydrate, lipid, and steroid metabolism, we investigated the relationships between liver pathology and the metabolic syndrome. Blood chemistry, anthropometry (waist/hip circumference ratio), and intraoperative routine knife biopsies of the liver were obtained in 551 (112 men) severely obese patients (body mass index, 47 +/- 9; mean +/- SD) undergoing antiobesity surgery. Steatosis was found in 86%, fibrosis in 74%, mild inflammation or steatohepatitis in 24%, and unexpected cirrhosis in 2% (n = 11) of the patients. The risk of steatosis was 2.6 times greater in men than in women (P < 0.0001). With each addition of 1 of the 4 components of the metabolic syndrome, elevated waist/hip ratio, impaired glucose tolerance, hypertension, and dyslipidemia, the risk of steatosis increased exponentially from 1- to 99-fold (P < 0.001). Fibrosis correlated with steatosis (r = 0.56; P < 0.0001), whereas patients with diabetes or impaired glucose tolerance had a 7-fold increased risk of fibrosis (P < 0.0001). Diabetes, steatosis, and age were all significant indicators of cirrhosis, whereas inflammation was only associated with age. We conclude that the metabolic syndrome via impaired glucose tolerance is strongly correlated with steatosis, fibrosis, and cirrhosis of the liver.

Overview of surgical techniques for treating obesity.

Nonsurgical methods fail to maintain clinically significant weight loss greater than or equal to 5 y in severely obese patients. Vertical banded gastroplasty and Roux-Y gastric bypass are the main operations for obesity. Modifications of intestinal bypass reserved for special cases require particular expertise in long-term management. Operations function by inducing satiety, nimiety, or aversion. Optimal weight loss or goal weights have not been defined and outcome predictors are inadequate. Results depend more on motivation and behavior than on metabolic, gastrointestinal, or technical factors. New approaches such as adding vagotomy or using inflatable cuffs to adjust outlet size in gastroplasty or modifying outlets or segment lengths in gastric bypass might improve long-term results. A staged approach to surgical treatment of obesity is proposed. Surgery will persist as a viable treatment alternative for severe obesity until effective preventive measures are taken to reduce the prevalence of this serious disease.

Refeeding after a fast in rats: effects on small intestinal enzymes.

The effect of resuming food intake after a period of starvation (refeeding) on the specific activities of selected rat intestinal enzymes was determined. The rate of weight gain was higher in refed animals than in control animals, without a difference in food intake. Fasting caused intestinal atrophy which reversed rapidly on refeeding. Fasting decreased the specific activities of sucrase, maltase, and galactokinase, but did not affect the specific activities of hexokinase, pyruvate kinase, or crypt thymidine kinase. Sucrase, maltase, hexokinase, pyruvate kinase, and thymidine kinase specific activities all rose above control values during refeeding. The overshoot in intestinal enzyme specific activities may help promote the rapid weight gain observed in refed rats and is an integral part of the total adaptation to fasting and refeeding.