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.

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.

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.

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.

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.

Differentiation of pancreatobiliary cancer from benign biliary strictures using neutrophil gelatinase-associated lipocalin.

Aim of the study was to investigate the value of serum and bile neutrophil gelatinase-associated lipocalin (NGAL) for distinguishing malignant strictures caused by cholangiocarcinoma (CCA) or pancreatic cancer from benign biliary strictures. The study was performed prospectively on patients admitted for endoscopic or radiologic biliary decompression. Forty patients with dilated biliary ducts, including 16 cases of CCA, 6 cases of pancreatic cancer, and 18 cases of benign biliary stricture were enrolled. Their sera and bile were collected to measure NGAL. Routine biochemistry including measurement of serum levels of carbohydrate antigens (CA) 19-9 and carcinoembryonic antigen (CEA) was also performed. The serum CA19-9, serum CEA, and bile NGAL levels were significantly increased in patients with malignant strictures as compared with patients with benign biliary diseases. Serum NGAL had no significant value for discriminating between malignant and benign biliary strictures. Bile NGAL levels had a receiver characteristic area under the curve of 0.74, sensitivity 77.3, and specificity 72.2% for discriminating between pancreatobiliary cancer and benign biliary diseases. Bile NGAL and serum CA19-9 were independent parameters and their combined use improved diagnostic accuracy (sensitivity 91%, negative predictive value 85.7%). We conclude that measurement of biliary, but not serum NGAL, may differentiate malignant pancreatobiliary from benign biliary strictures, serving as a complementary biomarker for serum CA19-9.

Biliary complications after orthotopic liver transplantation: a 5-year experience.

INTRODUCTION: Biliary complications, particularly bile duct stenosis or leak, remain the "Achilles' heel" of orthotopic liver transplantation (OLT), significantly increasing the risk of graft loss and recipient death. The aim of the study was to retrospectively analyze biliary complications over a 5-year experience seeking to identify risk factors for these complications. MATERIAL AND METHODS: Eighty-seven OLT performed in 84 recipients were included in the analysis. In all cases but one, we performed an end-to-end hepatic duct anastomosis with a 7-0 running suture under 2.5× magnification. RESULTS: Biliary complications developed after 17.2% OLT: anastomosis site stenosis (10.3%), multiple stenoses (5.7%), or bile duct necrosis (1.1%). A bile leak was not observed. Two recipients died from biliary sepsis. Among the patients with biliary complications, there was an higher rate of hepatic artery problems (33.3% vs 2.7%; P<.01), and a longer anhepatic phase (85 vs 72 minutes; P<.01). We performed endoscopic treatment in 73% and percutaneous drainage in 6.6% of recipients. Good treatment results were achieved in 36.4% of cases with biliary complications whereas they were satisfactory in 27.3%. Five patients with biliary complications required re-transplantation. CONCLUSIONS: A bile duct anastomosis performed end-to-end with a running suture under magnification decreased the risk of bile leakage after OLT. A prolonged anhepatic phase or an hepatic artery thrombosis or stenosis increased the risk of biliary complications after OLT.

Coagulopathy in liver diseases.

Liver cirrhosis is associated with number of hematological complications and coagulation disturbances. In view of various haemostatic abnormalities it is surprising that many patients do not bleed spontaneously. Severe coagulopathy of liver disease is more frequently seen in acute liver failure, but still remains important complication of liver cirrhosis and chronic liver failure. Decreased production of blood coagulation factors by the liver plays a key role in altered haemostasis in liver diseases. Altered fragile balance of blood coagulation proteins and infection are associated with both worsening coagulopathy and bleeding risk. Additional haemostatic abnormalities in patients with severe liver diseases are thrombocytopenia, chronic disseminated intravascular coagulation, accelerated fibrinolysis, hypofibrinogenemia and dysfibrinogenemia. In this review we discuss a complicated issue of multiple coagulopathies in patients with advanced liver dysfunction.

Non-endoscopic diagnosis of multifocal atrophic gastritis; efficacy of serum gastrin-17, pepsinogens and Helicobacter pylori antibodies.

BACKGROUND/AIMS: Infection with H. pylori is an important risk factor for the development of gastric cancer and glandular atrophy is an intermediate stage in gastric carcinogenesis. While screening the patients with atrophic gastritis by endoscopy is unrealistic, a concept of "serological gastric biopsy" based on measurement of gastric secretory proteins and peptides should be further validated. We sought to determine if the laboratory panel composed of serum PGI and protein stimulated gastrin-17 might select patients with MAG, and what is diagnostic significance of H. pylori serology in population of high prevalence of H. pylori infection. MATERIAL AND METHODS: 55 consecutive patients of both sexes (M/F 25/30; range of age 55 -81 years) were referred for gastroscopy with antrum and corpus mucosal biopsies. Patients with histological signs of glandular atrophy at any site of the stomach were considered to have multifocal atrophic gastritis. A first blood sample was collected for measurement of basal gastrin-17, pepsinogens and H. pylori IgG-antibodies, and second was taken 20 minutes after use of protein-rich drink to measure stimulated gastrin-17. RESULTS: Signs of mucosal atrophy were found in 19 patients, while 29 patients showed non-atrophic gastritis and seven H. pylori-negative patients had no histological pathology. Low serum level of stimulated gastrin-17 (< 5 pmol/l) and/or pepsinogen I (< 50 microg/l), were found in 16 of 19 patients (84.2%) with and in 7 of 36 patients (19.4%) without atrophy in the histological study. Combining of H. pylori serology with serum levels of secretory peptides had no significant effect on diagnostic sensitivity of the test panel. CONCLUSION: The test panel composed of pepsinogen I and protein stimulated gastrin-17 may be used as the "serological gastric biopsy" detecting multifocal atrophic gastritis. The diagnostic sensitivity of this test panel is not increased by knowledge of H. pylori status.

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.

[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.

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.

Effects of a spleen peptide preparation as supportive therapy in inoperable head and neck cancer patients.

Patients with inoperable head and neck cancer were treated with a spleen peptide preparation (Polyerga) in a phase III randomized, placebo-controlled double-blind study during chemotherapy (cisplatin/carboplatin, 5-fluorouracil) to investigate further the efficacy of this peptide preparation as supportive treatment under chemotherapy. Immunological changes as well as quality of life aspects were examined. Forty patients were included in this study. The peptide preparation had a significant stabilizing effect on the peripheral blood lymphocyte status during chemotherapy cycles (Student t-test, p = 0.05) and tended to stabilize the shift of granulocyte count (Student t-test, p = 0.18). In addition, the group receiving the verum showed a remarkable stabilization of body weight (Mann-Whitney U-test, p = 0.17) during chemotherapy treatment and the generally observed increase of fatigue-inertia during the chemotherapy cycles was significantly reduced (Student t-test, p = 0.01).

Neurogenic tumors of the digestive tract: report of two cases.

We report two female patients with neurogenic tumors of the digestive tract. In the first patient, the tumor of 10 cm diameter originated in the stomach and at preoperative CT imitated a peripancreatic cyst. In the second patient, the tumor of 6 cm diameter originated in the duodenum. Despite large size, the tumors were clinically indolent and escaped detection at routine endoscopic evaluation. In both cases the neoplasm was removed and postoperative histopathology combined with immunohistochemistry was consistent with diagnosis of digestive Schwannoma.

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.

Acute cholestatic hepatitis associated with pravastatin.

A 57-yr-old man presented with clinical and laboratory signs of acute cholestatic hepatitis. Symptoms had appeared 7 wk after he was started on pravastatin 20 mg/day for hypercholesterolemia. A full evaluation including ultrasound, computed tomography, endoscopic cholangiography, and liver biopsy confirmed the diagnosis of intrahepatic nonobstructive jaundice. The liver function abnormalities normalized 7 wk after cessation of therapy. Pravastatin should be considered as a potential cause of cholestatic hepatitis with favorable clinical outcome after drug withdrawal.