Pancreatic stellate cells - rising stars in pancreatic pathologies.

Pluripotent pancreatic stellate cells (PSCs) receive growing interest in past decades. Two types of PSCs are recognized -vitamin A accumulating quiescent PSCs and activated PSCs- the main producents of extracellular matrix in pancreatic tissue. PSCs plays important role in pathogenesis of pancreatic fibrosis in pancreatic cancer and chronic pancreatitis. PSCs are intensively studied as potential therapeutical target because of their important role in developing desmoplastic stroma in pancreatic cancer. There also exists evidence that PSC are involved in other pathologies like type-2 diabetes mellitus. This article brings brief characteristics of PSCs and recent advances in research of these cells.

Endoscopic ultrasound-guided fine needle aspiration biopsy of pancreatic lesions. An 8-year analysis of single institution material focusing on efficacy and learning progress.

OBJECTIVE: To evaluate the efficacy and the learning curve of the endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) diagnostics of pancreatic lesions over 8 years (2007-2014). MATERIAL AND METHODS: EUS-FNAB using a Linear Echoendoscope Olympus was performed in 531 patients, mostly without rapid on-site evaluation (ROSE). Smears plus cytoblock sections were used routinely. Immunocytochemistry was utilised as indicated. RESULTS: The average, satisfactory sampling rate increased from the 61.2% in the first 3-year period to 72.9% in the last 3-year period (P = 0.008). The availability of the material for cytoblocks increased from 36.4% in the first period to 75.3% in the last period (P = 0.017). The efficacy of cytoblocks increased from 39.6% to 46.2% (P = 0.086). Comparing the first and last 3-year periods, the indication for immunocytochemistry did not rise substantially (5.2% and 8.5% respectively), but the predictive value of immunocytochemistry rose from 56.3% to 100.0% (P = 0.001). The most frequent diagnostic result was malignancy confirmation - both primary (41.2%) and metastatic (2.1%). In cases with representative samples and follow-up information, the specificity, sensitivity, positive predictive value and accuracy were high from the beginning. The negative predictive value decreased slightly in the last 3-year period. CONCLUSION: The pancreatic EUS-FNAB without ROSE represents a suboptimal arrangement conditioned with our staff/time/location reality. Nevertheless, within the last 3 years of our activity, nearly three-quarters of patients profit from the diagnostic contribution of this procedure.

Treatment of locally advanced pancreatic cancer by percutaneous and intraoperative irreversible electroporation: general hospital cancer center experience.

The aim of this study was to evaluate the safety of irreversible electroporation (IRE) and the outcome of patients undergoing IRE of locally advanced pancreatic cancer (PC). Twenty-one patients with unresectable PC underwent open (n=19) or percutaneous (n=2) IRE of the tumor using the Nanoknife system with two electrodes that were repositioned several times to affect the whole mass. The size of the tumor was 39±10mm with a range from 21 to 65mm. Five patients underwent neoadjuvant chemotherapy and seven patients were treated with chemotherapy after IRE. Complications occurred in five patients, which resulted in prolongation of the average hospital stay from 10 to 34 days. There was no mortality in the first postoperative month. Median survival after IRE was 10.2 months compared to 9.3 months in a matched cohort (hazard ratio = .54, p = .053). The quality of life was declining slowly. 81% of time after IRE the Karnofsky performance status was ≥70 and sharp decline occurred approximately 8 weeks before death.In conclusion, IRE is a safe palliative treatment option for a percentage of patients with locally advanced pancreatic carcinoma. The patients treated with open IRE lived a decent life until 8 weeks before their death. We believe that IRE of pancreatic carcinoma can be regarded as an option, if imaging or explorative laparotomy show that R0 resection in not possible.

[Cystic tumors of the pancreas - - our experience with diagnostics]. / Cystické nádory pankreatu -  nase zkusenosti.

Number of newly diagnosed cystic pancreatic tumors is permanently increasing. This fact is primarily related to the development of new diagnostic methods. The main representative ones are: serous cystadenoma, mucinous cystic neoplasm, intraductal papillary mucinous neoplasm and solid pseudopapillar tumor. Because of the malignant potential of these lesions, proper indication of surgical treatment is extremely important. The article highlights and describes our experience in diagnostics and therapy of cystic pancreatic tumors diagnosed in the General Teaching Hospital Prague in the period: 1/ 2008- 12/ 2012. All patients were investigated by computerised tomography and endoscopic ultrasound with fine -  needle aspiration biopsy. Thirty seven patients in total were diagnosed with cystic pancreatic tumors: 19 with serous cystadenoma, 5 with mucinous cystic neoplasm, 5 with mucinous cystadenocarcinoma, 5 with intraductal papillary mucinous neoplasm and 3 with solid pseudopapillar tumor. In 14 cases patients were indicated for surgery, in 1 case signs of malignant transformation were found. Determination of the optimal strategy for diagnostic and therapeutic procedures in patients with cystic pancreatic tumors requires the dia-gnosis, treatment and followup observation in adequately equiped specialized centers.

Paraoxonase-1 (PON1) status in pancreatic cancer: relation to clinical parameters.

Human paraoxonase 1 (PON1) has been shown to decrease the level of systemic oxidative stress, which is thought to contribute to cancer development. The aim of this study was to examine the interrelationships between PON1 status and some clinical characteristics in patients with pancreatic cancer (PC). A group of 73 consecutive patients with PC (stage II-IV) and 73 control subjects were examined. Laboratory studies included five polymorphisms of the PON1 gene (L55M, Q192R, -108C/T, -126C/T, and -162A/G), PON1 arylesterase (PON1-A) and lactonase (PON1-L) activities, as well as some markers of protein metabolism, insulin resistance, and oxidative stress. In comparison with the control group, no difference in the distribution of the PON1 polymorphisms was found in cancer patients, both arylesterase and lactonase activities being significantly lower (-33, -47 %, respectively, both P < 0.001). There was neither statistically significant association of PON1 polymorphisms with tumour stages nor with diabetes mellitus connected with PC. The genotype distribution of L55M and ­108C/T differed only in a subgroup of patients presenting clinically relevant malnutrition (χ² = 6.50, 6.25, respectively, both P < 0.05). In the PC group, PON1-A and PON1-L activities correlated with Nutritional Risk Index (r = 0.351, 0.409, respectively, both P < 0.01), PON1-L with mid-arm muscle circumference (r = 0.328, P < 0.05), and PON1-A and PON1-L with serum albumin (r = 0.352, 0.391 respectively, both < 0.01). Our results suggest that PON1 plays an important role in PC, especially in cancer-associated malnutrition.

Leptin and adiponectin in pancreatic cancer: connection with diabetes mellitus.

UNLABELLED: The aim of this study was to analyze the relationship of serum leptin as well as adiponectin and the manifestation of pancreatic cancer (PC). Serum leptin, adiponectin, glucose homeostasis and insulin resistance (expressed as HOMA-IR) were investigated in 64 patients with newly diagnosed PC and compared with 64 healthy controls (CON group) and 75 patients with type 2 diabetes (DM2). Seventy percent of newly diagnosed PC patients had DM2. The levels of leptin were lower, whilst adiponectin/leptin ratio was higher in PC patients (both with and without DM2), in comparison with CON and DM2 groups (P < 0.001) independently of age, BMI and waist circumference. Newly diagnosed PC is characterized with lower leptin concentrations and higher adiponectin/leptin ratio in comparison with CON or DM2 individuals. Analysis of these parameters could help in the screening of persons in high risk for PC, especially in those with DM2. KEYWORDS: adiponectin, leptin, pancreatic cancer, type 2 diabetes mellitus.

Polymorphism -23HPhI in the promoter of insulin gene and pancreatic cancer: a pilot study.

Pancreatic cancer (PC) is one of the most frequent gastrointestinal malignancies with extremely poor prognosis. In spite of a relative low incidence of PC, in comparison with other cancers, PC is the fourth leading cause of cancer death in USA in both sexes. The available data clearly suggest that diabetes mellitus (DM) can be both a long-standing cause of PC and an early manifestation of the disease. Besides of DM, insulin resistance and high insulin levels are linked as well with increased cancer risk, including PC. The variable number of tandem repeats (VNTR) locus upstream of the insulin gene (INS) regulates insulin expression and has been associated with susceptibility to many diseases including DM. It is known that there is nearly complete linkage disequilibrium of the insulin variable tandem of repeats (INS-VNTR) alleles I/III with neighboring -23 HphI A/T single nucleotide polymorphism (SNP) in Caucasians. Therefore, we have studied the association between SNP of -23HphI in promoter of INS with PC, DM Type 2 (2TDM) and healthy controls. In this study we investigated 153 subjects (86 M/67 F); 51 patients with newly-diagnosed PC (31 M/20 F), 45 patients with 2TDM (29 M/16 F) and 57 healthy control subjects (26 M/31 F). The polymorphism of -23HphI (A/T) in the promoter of INS was determined by the combination of polymerase chain reaction (PCR) with the restriction fragment length polymorphism (RFLP) methods. The results obtained by the PCR-RFLP analyses of SNP -23HphI were confirmed by a direct studied locus sequencing of the genomic DNA. The frequency of abnormal glucose metabolism (both DM and impaired fasting glucose) was 88 % (45/51) in PC group. The AA genotype in SNP -23HphI was more prevalent (67 % vs. 47 %; P<0.05) among PC patients compared to controls. Additionally, statistically significant differences were found in frequencies (%) of genotypes AA/AT/TT in groups with PC (67/27/6), 2TDM (53/40/7) compared to healthy controls (37/46/17) (P<0.05). Moreover, a statistically significant effect of -23HphI A/T polymorphism on tumor staging was found (P< 0.05). Polymorphism of -23HphI (A/T) in the promoter of INS may play a role in the pathogenesis of PC and could contribute to tumor staging. Key words: pancreatic cancer; insulin gene regulation; polymorphism of -23HphI; diabetes mellitus; disorders of glucoregulation.

[Faecal elastase I--its use in diagnosis of chronic pancreatitis]. / Stanovení elastázy I ve stolici--vyuzití v diagnostice chronické pankreatitidy.

BACKGROUND: The diagnosis of chronic pancreatitis is based on the imaging methods. These imaging methods show the main morphological changes in the pancreatic ducts and its parenchyma, but they do not define the function of the pancreas. The aim of our study was Faecal Elastase I. determination in patients with chronic pancreatitis. The test is a simple, non-invasive method of the investigation of the pancreatic exocrine insufficiency. The Faecal Elastase I occurring in the stool was correlated with the level of the damage of pancreatic tissue together with the control group of the patients with different diagnoses. METHODS AND RESULTS: Faecal Elastase I (mean values in ug/g of stool) detection is a simple, non-invasive method which correlates well with the damage of pancreatic tissue, stemming from chronic pancreatitis. This test is routinely used especially in the diagnosis of chronic pancreatitis. The classification of chronic pancreatitis currently depends on the morphological changes of the pancreatic duct system (the patho-morphological changes). We are currently missing the classification describing simultaneously the morphological changes of the gland and the function of the pancreas. In our studies we have used a newly proposed classification system, which was put together in Bern, 2000 (1). This new system encompasses morphological and functional changes. Faecal Elastase I was determined by a microplate ELISA method using monoclonal antibody to human pancreatic protein. The Faecal Elastase I. was tested in the stool of the 196 patients with chronic pancreatitis stemming from alcoholism. The occurrence of Faecal Elastase I. was classified according to the levels assigned by the classification system. The control group used in this study included 144 patients with different diagnoses. The results demonstrate a very good correlation of Faecal Elastase I. with the grading of the newly proposed classification system of chronic pancreatitis. Patients with the highest levels of the damage of the pancreas had a significantly lower occurrence of Faecal Elastase I. in comparison with the non-pancreatic control group and in patients with chronic pancreatitis who had no clinical complications or damage of endocrine and exocrine functions of the pancreas. CONCLUSIONS: Feacal Elastase I performance plays an important role in diagnosing of the severe cases of chronic pancreatitis and in the follow-up of the chronic pancreatitis in the patients with the intermediate damage of the pancreas.

[Protective mechanism of the gastric mucosa]. / Ochranné mechanizmy zaludecní sliznice.

The gastric mucosa represents a masterpiece in the functional design. As the tissue lining the stomach, it secretes aggressive combination of digestive fluids, powerful enough to digest any tissue. Nonetheless, the gastric mucosa remains undamaged by the effect of its inherent protective mechanisms. The possibility of development of gastric erosions and ulcers remains vivid evidence that the gastric mucosa is not always resistant to injury.

[Pancreatic carcinoma and diabetes mellitus]. / Karcinom pankreatu a diabetes mellitus.

BACKGROUND: The aim of the present study was to evaluate the relationship between Pancreatic Cancer and Type 2 Diabetes Mellitus, which represents a higher risk of many human tumors. In patients with Pancreatic Cancer, Type 2 Diabetes Mellitus occurs approximately in 30%. METHOD AND RESULTS: Fifty patients with newly diagnosed Pancreatic Cancer were analysed in a retrospective pilot study where the staging of the tumor and the case history of the patients were studied. This data were compared in three groups of patients: the control group without diabetes, one with Impaired Fasting Glucose, and patients with Diabetes Mellitus. Incidence of Diabetes Mellitus and that of Impaired Fasting Glucose were also followed in patients with Pancreatic Cancer and Colorectal Cancer. The retrospective study confirmed the late diagnosis of Pancreatic Cancer. The tumors were actually in clinical stage IV in 50% of the patients. Diabetes Mellitus was present in 34% of patients with Pancreatic Cancer; in 44% of these patients the Impaired Fasting Glucose was also diagnosed while the normal glucose status was seen in 22% of patients. Incidence of Impaired Fasting Glucose and that of Diabetes Mellitus in groups of patients with Pancreatic Cancer and Colorectal Cancer was studied. Diabetes Mellitus was present in 12.5% patients with Colorectal Cancer. CONCLUSIONS: In spite of modern diagnostic methods, the early diagnosis of Pancreatic Cancer remains a great problem. Incidence of Diabetes Mellitus in patients with Pancreatic Cancer was significantly higher in comparison with the Colorectal Cancer group (P0.01). A significant number of patients with Impaired Fasting Glucose were also present in the group with Pancreatic Cancer. Analysis of the relationships between Pancreatic Cancer and Impaired Glucose Metabolism could contribute to the early diagnosis of this serious malignant disease.

[Helicobacter pylori infection and diseases of the stomach and duodenum]. / Problematika infekce Helicobacter pylori u chorob zaludku a duodena.

The last twenty years have been the witness of the major revolution in the medical science and practice. Pathogenesis of gastric ulcer disease has probably undergone the most serious change both in the conception and in practice. Though the number of information concerning Helicobacter pylori (Hp) is rising explosively, our understanding of the specific and detailed role of Hp infection in the pathogenesis of various Hp related diseases remains modest.

[Indication for the treatment of Helicobacter pylori infection]. / Indikace k eradikaci a lécbe infekce Helicobacter pylori.

Helicobacter pylori is a microorganism that is thought to play a role in the etiopathogenesis of peptic ulcer disease. Eradication of this microorganism is valuable clinical cure of infected patients. Efficacious regimens generally include an antisecretory agent combined with two antimicrobials. The main determinant of overall cost of treatment is the rate of eradication of the microorganism. Resistance can occur to the commonly used antibiotics but can usually be overcome with an altered regimen. It is important for care physicians to clearly understand indication and how to select appropriate therapy against Helicobacter pylori infection.

[Primary biliary cirrhosis--specific anti-mitochondrial antibodies]. / Primární biliární cirhóza--specifické antimitochondriální protilátky.

UNLABELLED: Primary biliary cirrhosis is a chronic liver disease, characterized by the destruction of the epithelial cells of the sublobular, interlobular and septal bile ducts and with the development of cirrhosis. The presence of anti-mitochondrial antibodies against the subunits of mitochondrial 2-oxoacids dehydrogenases is characteristic for patients with primary biliary cirrhosis. The aim of this work was to study the effect of anti-mitochondrial antibodies upon activity of the isolated mitochondrial pyruvate dehydrogenase complex after the incubation with serum from patients with primary biliary cirrhosis. GROUP OF PATIENTS AND METHODS: The activity of the purified bovine pyruvate dehydrogenase complex was studied spectrophotometrically in presence of the serum (1: 1000) from five patients with primary biliary cirrhosis and from ten disease free controls. RESULTS: The activity of the pyruvate dehydrogenase was decreased after incubation with the serum from patients with primary biliary cirrhosis. No similar inhibitory effect was found after incubation with serum from controls. DISCUSSION: The inhibitory effect of the anti-mitochondrial antibodies upon activity of pyruvate dehydrogenase may broaden the spectrum of diagnostic methods in patients with primary biliary cirrhosis. Further investigations are necessary to assess the possible application of this method for monitoring of changes during the course of the disease and for assignation of the disease prognosis.

[Statins in the treatment of tumors. Fiction or a new therapeutic approach?]. / Statiny v lécbe nádorových onemocnení. Fikce nebo nový terapeutický prístup?

HMG-CoA reductase inhibitors (statins) belong to the key hypocholesterolemic drugs. Besides this very important function, several others have been recently demonstrated such as the inhibition of atherogenous plaque formation, platelet aggregation, or improvement of endothelial function and fibrinolytic activity, or even the direct protective effects of statins on the mortality of acute myocardial infarction. Aside from the major interest of both the medical community and pharmaceutical companies remain the very important anti-tumor effects of this group of drugs. As based on recent medical research, inhibition of HMG-CoA reductase, the key enzyme in the cholesterol biosynthesis, brings about depletion of several intermediates. The most important one seems to be farnesyl pyrophosphate, which has a very important role in the cell signaling affecting apoptosis. The aim of the survey is to summarize present knowledge in this medical field and to demonstrate the enormous curative potential of this group of drugs.

[Effect of fasting on gastric mucosa thickness: experimental study in laboratory rats]. / Vliv hladovení na tloust'ku zaludecního hlenu: experimentální studie u laboratorních potkanu.

BACKGROUND: It has been proven that damage to the gastric mucosa is the result of the combined effects of acidopeptic agents including infection with Helicobacter pylori and insufficient protective mechanisms of the mucosa. Thickness of gastric mucus is very important protective factor. We can hypothetically expect that fasting may cause changes in the thickness of gastric mucus layer, which may in certain circumstances contribute to the conditions for mucosal injury. We have therefore conducted an experimental study on laboratory rats, aiming to assess the changes in the thickness of gastric mucus after 8 and 24-hour periods of fasting. METHODS AND RESULTS: We measured gastric mucus thickness with the aid of microelectrodes in 279 laboratory rats (group I) after 8 hours of fasting (2 measurements each, total of 558 measurements), followed by the same measurement in 70 laboratory rats (group II) after a 24-hour fasting. Group I had a gastric mucus thickness of 595 +/- 10 (mean +/- SD, microns); in group II the thickness was 502 +/- 10 (mean +/- SD, microns). After statistical analysis of the homogeneity of the two populations (Fisher's analysis), it has been proven that both groups belong to the same basic population sample. The statistical evaluation of the thickness of gastric mucus in both groups showed thinning of the mucus layer to 1% of the significant statistical difference. The difference between both groups is statistically significant. CONCLUSIONS: The thickness of gastric mucus is reduced after 24 hours' fasting in laboratory rats. This change is statistically significant (P < 0.01). It can be hypothesized that--under the specific conditions--this process can facilitate the injury of gastric mucosa.

[Spontaneous bacterial peritonitis in the Czech Republic]. / Spontánní bakteriální peritonitida v Ceské republice.

The objective of the study was to assess the prevalence and more detailed data pertaining to the incidence of spontaneous bacterial peritonitis (SBP) in the Czech Republic. The authors examined 99 patients with cirrhosis of the liver and ascites. SBP was diagnosed in a high percentage--35 patients, i.e. 35.4%. It was found more frequently in patients with an alcoholic etiology of cirrhosis who had a history of subfebrile and febrile temperatures and increasing trend of ascites. For the diagnosis the increase of leucocytes in serum and C reactive protein levels may prove useful. Lower values of total protein and albumin in ascites predispose to the development of this infection. Reduction of the number of thrombocytes in the group of patients with SBP indicates the influence of portal hypertension in the etiology of this disease.

[Laparoscopic fundoplication in the treatment of Barrett esophagus]. / Laparoskopická fundoplikace v lécbe Barrettova jícnu.

UNLABELLED: Barrett's esophagus (BE) the serious complication of gastroesophageal reflux disease (GERD) is discussed. BE has been defined as the complete intestinal metaplasia of distal esophagus. The most serious complication of BE is esophageal adenocarcinoma. We present our results with the group of patients with GERD from the years 1998-2000. We prospectively followed 67 patients with GERD (group A) and 8 patients with GERD/BE (group B). All patients underwent laparoscopic fundoplication. The average length of the Barrett's segment was 4.3 cm. Average time of the surgery was 75 min. Nissen fundoplication was used in seven cases in group B, in one case we used Rossetti laparoscopic fundoplication. The postoperative endoscopic controls were performed at two months after surgery and then every one-year. RESULTS: In one case we observed the complete reepithelization with the mixed spinocelullar and columnar components. We didn't observe any one case of histological deterioration. There was on any difference between two groups regarding the subjective complains. Six patients form group B reported complete disappearing of pyrosis. Two patients reported significant improvement, with very rare pyrosis or dysphagia. Our experience (together with the literature) proved the surgical antireflux therapy is very safe, very effective and with very long lasting effect. The effectivity of surgical therapy is increased by the laparoscopy. Described laparoscopic approaches can lead to the reepithelization of Barrett's metaplasia or, at least, they can diminish the symptoms without any long-term medication. Surveillance endoscopy and biopsy are strictly recommended in all patients with BE and also in the patients with BE after antireflux surgery. The intervals depend on the grade of dysplasia in metaplastic epithelium.

[The syndrome of the common channel of the choledochal duct and the duct of Wirsung]. / Syndrom spolecného kanálu d. choledochus a d. Wirsungi.

The problem of the rare anomaly of pancreatic ad bile ducts--common channel syndrome is discussed. On the demonstrated case the necessity of ERCP in obscure etiology of chronic pancreatitis is suggested and the principle++ of surgical treatment--disconnection of the bile duct and the formation of choledochojejunoanastomosis on the excluded loop--is demonstrated which solved the problem.

[Diagnosis and treatment of hepatic cysts]. / Diagnostika a lécba jaterních cyst.

Hepatic cysts are at the present time of widespread use of abdominal ultrasonography a frequent finding. The authors summarize contemporary diagnostic possibilities of liver cysts and submit variants of the therapeutic procedure in case of symptomatic liver cysts. They present their own experience with the treatment of hepatic cysts by the evaluation method combined with administration of 96% ethanol into the cyst. They compare this therapeutic procedure with the method of simple evaluation of the contents of the cyst. The method of evaluation of hepatic cysts under ultrasonographic control with subsequent administration of 96% alcohol appears to be more successful from the aspect of the long-term effect, manifested by the disappearance of clinical symptoms and non-refilling of the cyst.

[Detection of point mutations on the Ki-ras gene using the PCR technique]. / Detekce bodové mutace na Ki-ras genu PCR technikou.

Present study was undertaken to detect Ki-ras point mutation at codon 12 in pancreatic adenocarcinomas (CaP) using the polymerase chain reaction-restriction fragment lengths polymorphism (PCR-RFLP). Three modifications of PCR-RFLP were performed with a mismatched primers creating a recognition site with only one allelic from (wild or mutated). Using two-step PCR-RFLP and two modifications of one-step PCR-RFLP we examined 5 resected adenocarcinomas of pancreas, 6 pancreatic juices and one DNA sample from peripheral blood of patient with generalized stadium of CaP. We compare all techniques and conclude, that the very sensitive two step PCR-RFLP is a suitable method for detection point mutations and eliminates the need for either oligonucleotide hybridization or DNA sequencing.