Pharmacological and dietary factors in prevention of colorectal cancer.

Colorectal cancer (CRC) is the third most prevalent neoplasm worldwide and fourth most frequent reason of cancer-related death throughout the world. About 70% of malignant tumors are related to lifestyle and environmental factors, and better knowledge of their significance might reduce the prevalence of CRC. The cyclooxygenase-2 (COX-2) inhibitory and other direct and indirect pathways of aspirin are translated to inhibition proliferation and enhanced apoptosis of cancer cells. Many studies showed the benefits of aspirin in reducing the risk of CRC development, cancer-related mortality and adenoma prevalence rate in general population, but not in high risk populations. The role of sulindac in CRC prevention is uncertain and the use of this drug is rather uncommon. Celecoxib - COX-2 selective inhibitor- showed efficacy in decreasing of colon adenoma recurrence only in some studies. The protective role of microelements is controversial. The beneficial effects of supplementation of selenium, calcium, folic acid, methionine, antioxidant supplements and probiotics are still not certain. A high energy diet consisting of red meat, animal fat, highly processed foods and unsaturated fats increases the risk of CRC. Carcinogenic role of fat and cholesterol depends on increased production of primary bile acids. The importance of milk and dairy products in CRC prevention is controversial. Fruits, vegetables and grain are considered to have protective effects against adenoma and CRC. Excessive alcohol consumption, smoking, physical inactivity are considered as important CRC risk factors. This article briefly summarizes current state of knowledge about the role of pharmacological and dietary prevention of colorectal cancer. Moreover, it indicates that despite many studies some aspects of this issue are not clear and require future studies.

Serum neutrophil gelatinase-associated lipocalin (NGAL) correlates with clinical and endoscopic activity in ulcerative colitis but fails to predict activity in Crohn's disease.

Serum neutrophil gelatinase-associated lipocalin (NGAL) is a low molecular weight protein released from activated neutrophils and intestine epithelium whose mRNA expression is increased in inflamed intestinal tissue. The purpose of this study was to explore the relationship between serum NGAL level and activity of inflammatory bowel diseases. A total of 120 patients, 79 with Crohn's disease (CD) and 41 with ulcerative colitis (UC) were prospectively included into the study. Serum NGAL was measured by ELISA. The inflammatory activity of UC was assessed by Mayo score and of CD by CDAI and SES-CD scoring systems. Increasing endoscopic severity of UC from remission/mild to moderate/severe was associated with increasing NGAL levels from 46.9 to 66.4 ng/ml (P = 0.002). NGAL concentrations were significantly lower in patients with complete endoscopic and histologic remission than in the active UC (46.9 versus 66.4 ng/ml, P = 0.009). Also deterioration of the clinical activity of UC patients was associated with increasing level of NGAL from 44.9 in remission/mild to 68.0 ng/ml in moderate/severe grade (P = 0.002). NGAL levels correlated with CRP (r = 0.49), ESR (r = 0.48) and iron concentrations (r = -0.63), but not with faecal calprotectin. NGAL showed ability to distinguish endoscopically active from inactive UC with AUC-ROC of 0.758 (sensitivity 96% and specificity 54%). However NGAL levels showed no significant relationship with either clinical or endoscopic activity of CD. We conclude that serum NGAL level corresponds to clinical and endoscopic activity of UC and accurately predicts disease endoscopic remission.

Fibroblast growth factor-21 and omentin-1 hepatic mRNA expression and serum levels in morbidly obese women with non-alcoholic fatty liver disease.

Fibroblast growth factor-21 (FGF21) and omentin-1 have been recognized as potent antidiabetic agents with potential hepatoprotective activity. The aim of this study was to evaluate hepatic FGF21 and omentin-1 mRNA expression as well as their serum levels as predictive markers of liver injury and insulin resistance in morbidly obese women with non-alcoholic fatty liver disease (NAFLD). This study included 56 severely obese women who underwent intraoperative wedge liver biopsy during the bariatric surgery. Hepatic FGF21 and omentin-1 mRNA were assessed by quantitative real-time PCR, while their serum concentrations were measured with commercially available enzyme-linked immunosorbent assays. The FGF21 serum level was significantly higher in patients with a greater extent of steatosis (grade 2 and 3) compared to those without or with mild steatosis (grade 0 and 1) (P = 0.049). Receiver Operating Characteristic analysis, however, showed poor discriminant power for the FGF21 serum levels in differentiating between more and less extensive steatosis with an AUC = 0.666. There was a tendency towards higher levels of hepatic FGF21 mRNA in patients with lobular inflammation and fibrosis and towards lower levels in the case of hepatocyte ballooning and steatosis. There was a positive mutual correlation between hepatic FGF21 and omentin-1 mRNA levels (r = 0.78; P < 0.001). Fibrosis stage was associated with serum glucose and homeostatic model assessment for insulin resistance (HOMA-IR) (P = 0.03 and P = 0.02, respectively). Serum omentin-1 was not associated with histopathological features. The hepatic omentin-1 mRNA levels showed a tendency to be lower in patients with advanced steatosis and hepatocyte ballooning. In conclusion, our study, which focused on hepatic FGF21 and omentin-1 mRNA expression, confirmed marked expression of both molecules in the liver of morbidly obese patients with NAFLD. More extensive steatosis was associated with evident changes in the serum FGF21 concentration in morbidly obese women with NAFLD, but the difference did not reach statistical significance. The vast amount of fat, both visceral and subcutaneous, in severely obese patients may be the additional source and influence the FGF21 and omentin-1 serum levels.

Influence of an upright body position on the size of intrapulmonary blood shunts in patients with advanced liver cirrhosis.

Hepatopulmonary syndrome (HPS) is a complication of liver cirrhosis and is responsible for chronic hypoxemia and its negative health consequences. The most relevant diagnostic criterion of HPS is evidence of pathological intrapulmonary blood shunting (IPBS). There is still insufficient knowledge about the subclinical forms of HPS. The aim of this study was to determine whether an erect posture in patients with liver cirrhosis had a significant effect on IPBS, the diagnosis of HPS and oxygen saturation. Thirty cirrhotic patients considered for liver transplantation were enrolled in this study. Pulse oximetry and lung perfusion scintigraphy were conducted in patients while they were in supine and upright body positions. Pathological IPBS was observed in 16% and 20% of patients examined in the supine and upright body positions, respectively (mean difference 0.59%; P = 0.046). Postural-related IPBS changes were markedly greater in patients with HPS (1.76%; P = 0.011). Oxygen saturation was significantly lower in the erect posture compared to the supine posture (mean difference 1.2%; P = 0.02); however, there was no relationship between oxygen saturation and IPBS. In conclusion, an erect posture in patients with advanced liver cirrhosis leads to a subtle increase in IPBS, which is more pronounced in patients with HPS, and oxygen saturation measurements are not sensitive enough to detect these changes.

Porcine splenic peptides (Polyerga) decrease the number of experimental lung metastases in mice.

Preparations of splenic peptides under the name of Polyerga are being tested in numerous experimental immunomodulating and antitumorous models and are also used during supportive treatment of tumorous patients. Further, the incidence of experimental lung metastases of melanoma cells in mice was significantly reduced if we used Polyerga preparations. The aim of our investigation was to determine whether Polyerga is active directly against tumor cells or whether its activity is manifested by modulating immune and other possible abilities of the organism. To clarify the problem glycopeptides containing Polyerga were incubated with melanoma B16F10 cells in vitro and the plating efficiency of these cells determined when cultivated in medium, or in medium with different doses of the same Polyerga preparation. The cells preincubated in medium only reacted to the addition of increasing doses of Polyerga, 150 pg or more, by raising colonies number. However, 24-h incubation of melanoma cells in the presence of 150 micrograms of Polyerga per ml significantly reduced the number of tumor cell colonies in comparison to the corresponding cell cultures previously not exposed to Polyerga. These in vitro studies were extended to in vivo application using C57B1/GoZgr mice injected i.v. with melanoma cells pretreated with Polyerga in vitro or previously not treated. A group of the treated mice was further injected i.p. with Polyerga. All the mice were killed at a particular time and the number of lung nodules determined. A significant difference to the control values was noticed in each group that used Polyerga, regardless of the exposure of melanoma cells to Polyerga in vitro, in vivo or to combined treatment. The efficiency of Polyerga application 7 days following i.v. injection of control melanoma cells (cultivated in medium only) when the nodules already exist, was further evaluated in a combined treatment using DTIC, a drug of choice in melanomas. The smallest incidence of experimental lung metastases was observed in the group exposed to the combination of DTIC and Polyerga. Polyerga preparation is thus active against melanoma cells, particularly in vivo and if combined with chemotherapy.

A modified E-rosette assay as a semi-empirical tool in search of new T lymphocyte stimulants.

An "activity index" is defined for T cell modulators, which allows meaningful comparison of experimental results by eliminating the deviations due to differences in the immunological states of T lymphocytes.

Severe hepatic involvement in visceral larva migrans.

Because of its anatomical position, the liver may be involved in many protozoan and helminthic gastrointestinal infections. Visceral larva migrans caused by Toxocara canis is rarely taken into account in adult patients with cholestatic syndrome, especially when liver disease is not associated with hypereosinophilic reaction. We report on a 74-year-old immunocompetent woman who presented with fever, bronchospasm, erythema nodosum, weight loss and progressive jaundice. A liver biopsy showed caseating granulomatous hepatitis with secondary portal fibrosis and paucity of interlobular bile ducts. A step-by-step search for aetiological factors led us to a diagnosis of toxocariasis (positive enzyme-linked immunosorbent assay IgG test). An excellent clinical response to combined treatment with steroid and diethylcarbamazine, and a reduction in the antibody level against T. canis supported the diagnosis. Computed tomography and laparoscopy demonstrated multiple small mass lesions and fibrous perihepatitis. This report shows that visceral larva migrans may be a cause of prostrating chronic liver disease and should be suspected in every febrile patient with cryptogenic cholestatic hepatitis.

Usefulness of thoracic electrical bioimpedance in detection of ejection fraction changes.

The aim of this study was to evaluate a usefulness of thoracic electrical bioimpedance (TEB) in following adaptive haemodynamic adjustments to postural change and isometric exercise. Sixteen subjects with intact cardiovascular system took part in this study. Haemodynamic parameters were obtained in recumbency and after taking up erect posture. Besides, TEB was performed during handgrip test and the results were compared with baseline resting data. Each time the radionuclide ventriculography (RV) was performed concurrently with TEB to obtain an independent measurement of ejection fraction (EF). Active orthostasis was associated with a change in stroke volume, cardiac output and total vascular resistance by -29.7%, -3.4%, +3.9%, respectively. The handgrip produced a significant increase in cardiac output by 16.3%, however it was not associated with an enhancement of stroke volume. Although there was a moderate correlation between EF calculated by TEB and RV in supine position (r=0.66; p < 0.001), TEB failed to reflect changes of EF in orthostasis and isometric exercise. In conclusion, our results suggest that TEB offers in subjects with normal cardiovascular function a valuable alternative to cardiovascular monitoring of stroke volume and cardiac output, but calculation of EF is associated with a risk of serious error.

Spleen peptides (Polyerga) inhibit development of artificial lung metastases of murine mammary carcinoma and increase efficiency of chemotherapy in mice.

There are numerous attempts to find novel anticancer drugs or to improve therapeutic protocols based on application of chemotherapeutic agents and immunomodulators (biological response modifiers, cytokines, various plant or bacterial products). Among the preparations that have beneficial effects for the cancer bearing organism are preparations of spleen peptides (Polyerga). Hence, we analyzed if treatment with spleen oligopeptides GP-1 (active substance for the manufacture of Polyerga ampoules' solution injected as 0.5 microgram/kg every second day) if given alone or combined with chemotherapy (Endoxan 50 mg/kg single i.p. dose) of mice bearing artificial lung metastases of mammary carcinoma will have an impact on the metastases count and survival of the animals. The results obtained have shown that chemotherapy reduced metastases count and increased survival of the tumor bearing mice, while the use of GP-1 alone did not affect metastases development. However, combined GP-1 treatment and chemotherapy were more efficient in prevention of the metastases development than chemotherapy alone. Thus, in mice treated with GP-1 and Endoxan, the average metastases count was four times lower than in the mice treated by chemotherapy only, while 2/12 animals were without tumor nodules in the lungs. Finally, all the animals treated by chemotherapy alone died until the 42nd day after tumor transplantation, while at the same time, only 5/10 animals died receiving combined therapy. Thus, these results give an experimental support for the use of the spleen peptides in biotherapy (or combined therapy) of cancer.

Evidence of improvement in deficient gastroenterological diagnosis--a regional experience report.

A similar study carried out in 1964-1975 showed that very low diagnostic efficiency in gastroenterology rose at the end of this period, supposedly due to the introduction of modern techniques. The present study was designed to evaluate the effect of new imaging techniques (computerized tomography, ultrasonography, gammagraphy and ERCP) in the routine diagnostic efficiency in the same department of gastroenterology between 1979-1983. The study was carried out in two series. In the first, 217 clinical diagnoses were compared with the autopsy findings, and 488 with the surgical findings in the second series. Diagnostic efficiency proved to be twice as high as 10 years ago (p less than 0.0005); the highest diagnostic level was attained in the upper digestive tract. The threefold improvement in pancreatic disease diagnosis from 22% in the previous study to about 60% now did not attain the same level of accuracy (p less than 0.001). The success was due to a 50% decrease (p less than 0.0005) in the number of false negative diagnoses, while false positives remained at the same level of about 10%. In contrast to earlier findings no great difference was found between younger and older age groups.

Focal liver disease: neural network-aided diagnosis based on clinical and laboratory data.

OBJECTIVES: The purpose of this study was to evaluate the use of clinical and laboratory data in the diagnosis of benign or malignant focal liver disease. METHODS: Diagnosis was made by artificial neural network (NN), a system of simple computing units connected in a specific structural network. Seven clinical and laboratory variables were retrospectively studied in 172 patients with a liver mass (93 benign, 79 malignant) detected with ultrasound. The diagnostic efficacy of NN was compared with a score based on the logistic regression model (Beaujon score). RESULTS: Although the sensitivity of the Beaujon score and the neural network was similar (4 malignant tumors inversely classified), neural network-aided diagnosis was characterized by higher specificity and accuracy (respectively 98.9% vs 82.5%, P < 0.001, and 97.1% vs 88.4%, P < 0.002). CONCLUSION: In patients with a hepatic mass, neural network is a valuable method for differentiating malignant and benign tumors.

[Relationships between plasma concentrations of endothelin and the severity of liver cirrhosis]. / Relations entre les concentrations plasmatiques d'endothéline et la sévérité de la cirrhose.

OBJECTIVES: Results of studies on plasma endothelin concentrations in patients with cirrhosis are conflicting. Moreover, the relationships between plasma endothelin concentrations and the severity of cirrhosis have not yet been studied. The aim of this study was to measure plasma endothelin concentrations in controls and in patients with cirrhosis. In addition, this study examined the relationships between plasma endothelin concentrations, and the severity of liver disease, splanchnic and systemic hemodynamics. METHODS: Plasma endothelin concentrations (in the hepatic vein and the right atria), hepatic venous pressures, arterial pressure, cardiac output, pulmonary pressures and plasma concentrations of sodium and creatinine were measured in 7 controls and 28 patients with cirrhosis. RESULTS: Plasma endothelin concentrations in the hepatic vein and the right atria were significantly higher in patients with cirrhosis (18.9 +/- 2.9 and 20.2 +/- 3.1 pg/mL, respectively) than in controls (6.1 +/- 1.1 and 7.2 +/- 1.1 pg/mL, respectively). In these patients, hepatic venous plasma endothelin concentrations were significantly correlated with Pugh's score (r = 0.49), hepatic venous pressure gradient (r = -0.44), and plasma sodium concentrations (r = -0.46). No significant correlation was found between plasma endothelin concentrations and systemic hemodynamics. CONCLUSION: Plasma endothelin concentrations are increased in patients with cirrhosis. Moreover, this increase is more marked in patients with severe liver disease than in patients with no or moderate impairment of liver function.

Cardiovascular changes after treatment with dexfenfluramine and yohimbine in obese women measured by thoracic electrical bioimpedance.

An anorectic drug, dexfenfluramine (dF) is commonly used in obesity treatment. The aim of our study was to investigate if dexfenfluramine used alone or together with alpha 2-adrenolitic yohimbine (Y), can change cardiovascular state in obese women.

[Giant hepatic hemangioma--diagnostic value of radioisotope investigations]. / Olbrzymi naczyniak watroby--wartosc diagnostyczna badan izotopowych.

In an example of a 60-year-old female patients with a giant hepatic haemangioma the authors discuss the diagnostic possibilities of radioisotope angiography in the detection of this vascular pathology. In confrontation with ultrasonographic examinations, computerized tomography, laparoscopy and even coeliac angiography only later hepatic scintigraphy using labelled erythrocytes was of decisive diagnostic importance.

[Primary sclerosing cholangitis and primary biliary liver cirrhosis as the causes of intrahepatic cholestasis]. / Pierwotne stwardniajace zapalenie dróg zólciowych i pierwotna marskosc zólciowa, jako przyczyny cholestazy wewnatrzwatrobowej.

Primary sclerosing cholangitis and primary biliary cirrhosis are rarely diagnosed diseases which should, however, be considered in the diagnosis of cholestasis. The authors present an outline of the modern knowledge on these diseases with particular reference to differential diagnosis.

[Chylous ascites following resection of abdominal aortic aneurysm]. / Puchlina mleczowa po zabiegu resekcji tetniaka aorty brzusznej.

Chylous ascites is an extremely rare complication of abdominal aortic surgery. We report on a case of chyloperitoneum following resection of aortic aneurysm. The diagnosis of lymphatic tear was confirmed by paracentesis which revealed milky fluid characterized by very high content of triglicerydes. Conservative management with a low-fat diet and diuretics resulted in a successful outcome.

[Angiographic findings in hereditary hemorrhagic teleangiectasia: a case study of Rendu-Osler-Weber disease]. / Diagnostyka angiograficzna nawracajacych krwawien z przewodu pokarmowego; opis przypadku choroby Rendu-Osler-Webera.

A case of Rendu-Osler-Weber disease in 48 year old male was described. Selective arteriography of superior mesenteric artery revealed its widening (including intestine branches), numerous anastomoses in the form of microhaemangioma and fast venous return with broad superior mesenteric and portal vein.

[Isotope methods in diagnosis of portal vein occlusion]. / Metody izotopowe w diagnostyce niedroznosci zyly wrotnej.

The dynamic intravenous hepato-scintigraphy with pertechnetate Tc-99m enables a quantitative evaluation of portal and arterial blood flow in the liver. A case is presented of thrombotic occlusion of the portal vein with rapidly growing oesophageal varices in which hepato-scintigraphy showed the absence of portal blood flow in the liver, being the decisive diagnostic method. Using the dynamic transrectal porto-scintigraphy an evaluation was done of the degree of collateral circulation development in the area of the inferior mesenteric vein, obtaining indirect information about localization and duration of portal vein occlusion.

13C-methacetin breath test correlates with clinical indices of liver disease severity in patients with primary biliary cirrhosis.

This prospective study intended to ascertain if cytochrome P450 dependent liver function is affected in early and late histological stages of primary biliary cirrhosis (PBC). The study included 32 female PBC patients (mean age 55.4 years, range 33-70) and 16 aged-matched healthy women (mean age 52.6 years, range 38-65). In every subject a 13(C)-methacetin breath test (13(C)-MBT) was applied, and the results were related to histological Ludwig's staging system and several indices of liver disease severity comprising the MAYO-1, MAYO-2, MELD, and Child-Pugh score. The 13(C)-MBT differentiated healthy controls from the patients with Ludwig IV and Ludwig III histopathological stages of PBC. The most significant relationships (i.e. explaining >50% of the variance) were found between measurements of the momentary breath 13(C) elimination from 6 to 18 minutes as well as the 15-min or 30-min cumulative elimination and the MAYO-1 or MAYO-2 scores. The breath test poorly correlated with histopathological features of PBC, however, it accurately discriminated cirrhotic from non-cirrhotic patients (momentary breath 13(C) elimination at 40 min, AUROC 0,958). In conclusion, 13(C)-MBT correlates with clinical scoring systems, especially those specifically designed for PBC (Mayo model) and accurately recognizes the disease at the stage of cirrhosis up to 40 minutes of the test duration.