Methylene blue chromoendoscopy is more useful in detection of intestinal metaplasia in the stomach than mucosal pit pattern or vessel evaluation and predicts advanced Operative Link on Gastric Intestinal Metaplasia stages.

BACKGROUND/AIMS: Intestinal metaplasia (IM) of the stomach is a precancerous condition that is often not visible during conventional endoscopy. Hence, we evaluated the utility of magnification endoscopy and methylene blue (MB) chromoendoscopy to detect IM. METHODS: We estimated the percentage of gastric mucosa surface staining with MB, mucosal pit pattern, and vessel visibility and correlated it with the presence of IM and the percentage of metaplastic cells in histology, similar to the Operative Link on Gastric Intestinal Metaplasia (OLGIM) stage. RESULTS: IM was found in 25 of 33 (75.8%) patients and in 61 of 135 biopsies (45.2%). IM correlated with positive MB staining (p<0.001) and other than dot pit patterns (p=0.015). MB staining indicated IM with better accuracy than the pit pattern or vessel evaluation (71.7% vs. 60.5% and 49.6%, respectively). At a cut-off point of 16.5% for the MB-stained gastric surface, the sensitivity, specificity, and accuracy of chromoendoscopy in the detection of advanced OLGIM stages were 88.9%, 91.7%, and 90.9%, respectively. The percentage of metaplastic cells detected on histology was the strongest predictor of positive MB staining. CONCLUSION: MB chromoendoscopy can serve as a screening method for detecting advanced OLGIM stages. MB mainly stains IM areas with a high concentration of metaplastic cells.

Elevated levels of soluble glycoprotein V - The plasma marker of platelet activation by thrombin in patients with early stage primary biliary cholangitis (PBC).

PURPOSE: There is a growing body of evidence for a prothrombotic tendency in patients with primary biliary cholangitis (PBC). The aim of the study was to evaluate coagulation disorders in patients with early stage PBC compared to healthy controls and evaluation of their relationship with clinical data, with particular emphasis on minimal hepatic encephalopathy (MHE). PATIENTS AND METHODS: Fifty-one participants (PBC group - 38 patients, all patients but one Child-Pugh A; control group - 13 healthy controls) were included in our prospective, single center study. We assessed the plasma levels of sGPV, plasma procoagulant phospholipids (PPL) and rotational thromboelastometry (ROTEM) profiles in all study participants. Porto-systemic encephalopathy syndrome test was used to assess MHE. RESULTS: The sGPV levels were higher in the PBC group compared to the controls: 36.07 â€‹± â€‹11.32 â€‹ng/mL vs 27.04 â€‹± â€‹11.72 â€‹ng/mL, p â€‹= â€‹0.031. The PPL level was lower in the PBC group compared to controls resulting in increased clotting time in a factor Xa-based coagulation assay: 54.65 (47.83-58.83) sec. vs 45.90 (43.3-50.5) sec., p â€‹= â€‹0.0065. PPL levels were correlated with platelet count (rho â€‹= â€‹-0.46, p â€‹= â€‹0.001). ROTEM parameters did not differ significantly between groups. Coagulation parameters did not differ significantly between patients with and without MHE. CONCLUSIONS: We have showed increased levels of sGPV - a plasma marker of platelet activation by thrombin in patients with early stage PBC compared to healthy controls. We found no relationship between the coagulation disorders and the occurrence of MHE. The PPL level was lower in the PBC group.

Comparative Effectiveness of Various Eradication Regimens for Helicobacter Pylori Infection in the Northeastern Region of Poland.

PURPOSE: Due to the lack of systematic data on antibiotic sensitivity, the treatment of the highly prevalent and pathogenic Helicobacter pylori (H. pylori) infection still poses a significant problem. Therefore, the aim of our study was to compare the efficacy of the three most commonly used anti-H. pylori therapies in northeastern Poland. PATIENTS AND METHODS: This was a retrospective, single-center study performed on 289 outpatients with an H. pylori infection. Patients received one of the following three treatment regimens: (1) bismuth quadruple therapy (BQT) for 10 days, (2) metronidazole-based triple therapy (M-TT) for 10 or 14 days, and (3) levofloxacin-based triple therapy (L-TT) for 10 or 14 days. RESULTS: BQT, M-TT, and L-TT accounted for 93.2% of prescribed anti-H. pylori therapies. The overall success rate for all treatment regimens was 84.1% (243/289). The effectiveness of first- and second-line therapy was similar and reached 83.8% and 86.2%, respectively. The efficacy of the individual treatment regimens was as follows: (1) BQT-89.4% (84/94), (2) M-TT-80.6% (112/139) and 78.8% (26/33) for 10 and 14 days, respectively, and (3) L-TT-84.6% (11/13) and 100% (10/10) for 10 and 14 days, respectively. The overall duration of treatment and type and dose of proton pump inhibitor (PPI) had no effect on the treatment efficacy. CONCLUSIONS: In the northeastern part of Poland, 10-day BQT and 10- or 14-day L-TT are effective treatment regimens for H. pylori eradication and have appear to be superior to M-TT. Practitioners in our clinic followed mostly local anti-H. pylori therapy guidelines.

The development of cigarette smoke induced chronic pancreatitis in mice is associated with increased expression of K-Ras and NF-κB.

INTRODUCTION AND OBJECTIVE: Epidemiological studies have demonstrated a strong association between cigarette smoking (CS) and chronic pancreatitis (CP); however, the exact mechanisms of this phenomenon remains unknown. The authors have previously shown that increased Ras expression activates the NF-κB mediated pathway and promotes development of CP. However, it is unclear whether a similar phenomenon occurs in CS-induced CP. Therefore, the aim of the study was to determine whether CS increases the expression of K-Ras, and promotes the development of CP in mice exposed to repeated episodes of acute pancreatitis (AP). MATERIAL AND METHODS: C57BL6/cmdb mice were exposed to CS or a sham treatment for 12 weeks. After one week of exposure, half of the animals from both groups were additionally subjected to repeated cerulein treatment (once a week, for 10 consecutive weeks) to mimic recurrent episodes of AP. Extension of pancreatic damage was determined histologically by H&E and Trichrome staining. The expression of K-Ras protein and downstream components (NF-κB, Cox-2, TGF-ß) was evaluated by immunohistochemistry. RESULTS: C57BL6/cmdb mice exposed to CS or cerulein alone did not develop any chronic pancreatic damage. However, concomitant treatment with both of these agents caused focal acinar atrophy, with slight intralobular and perivascular areas of fibrosis, and inflammatory cells infiltration resembling mild CP. Moreover, immunohistochemistry examinations revealed increased pancreatic expression of K-Ras and NF-κB only in mice treated both with CS and cerulein. CONCLUSIONS: CS promotes development of CP in mice exposed to repeated episodes of AP. This process may be, at least partially, related to increased expression of K-Ras and NF-κB protein.

Expression of VEGF, EGF, and Their Receptors in Squamous Esophageal Mucosa, with Correlations to Histological Findings and Endoscopic Minimal Changes, in Patients with Different GERD Phenotypes.

BACKGROUND: Gastroesophageal reflux disease (GERD) may present as nonerosive reflux disease (NERD), erosive esophagitis (EE), or be complicated by Barrett's esophagus (BE). The explanation as to what determines the phenotype of GERD is awaited. Therefore, we assessed the correlation between the growth factors expression and endoscopic as histologic findings in GERD patients. METHODS: The squamous esophageal epithelium of 50 patients (20-NERD, 7-EE, 15-BE, 8 controls) was examined by: (1) magnification endoscopy with evaluation of minimal GERD changes such as: microerosions, white spots, palisade blood vessels visibility, and intrapapillary capillary loops (IPCLs) appearance, (2) histology, (3) immunohistochemistry with evaluation of the expression of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and their receptors (VEGFR and EGFR). RESULTS: The expression of VEGF, but not VEGFR, EGF, and EGFR, was significantly increased in EE patients compared to NERD patients and controls. VEGF levels correlated significantly with the presence of white spots, but not with other minimal endoscopic and histologic features. The EGFR expression correlated positively with basal cell hyperplasia and enlarged IPCLs. CONCLUSIONS: Our findings suggest a correlation between growth factors expression and findings in conventional endoscopy, formation of endoscopic minimal changes, and histologic lesions.

Endoscopic management of leaks and fistulas after bariatric surgery: a systematic review and meta-analysis.

BACKGROUND: Endoscopic techniques have become the first-line therapy in bariatric surgery-related complications such as leaks and fistulas. We performed a systematic review and meta-analysis on the effectiveness of self-expandable stents, clipping, and tissue sealants in closing of post-bariatric surgery leak/fistula. METHODS: A systematic literature search of the Medline/Scopus databases was performed to identify full-text articles published up to February 2019 on the use of self-expandable stents, clipping, or tissue sealants as primary endoscopic strategies used for leak/fistula closure. Meta-analysis of studies reporting stents was performed with the PRISMA guidelines. RESULTS: Data concerning the efficacy of self-expanding stents in the treatment of leaks/fistulas after bariatric surgery were extracted from 40 studies (493 patients). The overall proportion of successful leak/fistula closure was 92% (95% CI, 90-95%). The overall proportion of stent migration was 23% (95% CI, 19-28%). Seventeen papers (98 patients) reported the use of clipping: the over-the-scope clips (OTSC) system was used in 85 patients with a successful closure rate of 67.1% and a few complications (migration, stenosis, tear). The successful fistula/leak closure using other than OTSC types was achieved in 69.2% of patients. In 10 case series (63 patients), fibrin glue alone was used with a 92.8-100% success rate of fistula closure that usually required repeated sessions at scheduled intervals. The complications of fibrin glue applications were reported in only one study and included pain and fever in 12.5% of patients. CONCLUSIONS: Endoscopic techniques are effective for management of post-bariatric leaks and fistulas in properly selected patients.

Laboratory evidence for hypercoagulability in cirrhotic patients with history of variceal bleeding.

AIM: We aimed to assess the relationship between procoagulant imbalance and the occurrence of variceal bleeding in patients with liver cirrhosis. METHODS: We compared the results of chromogenic assay for the functional evaluation of the Protein C anticoagulant pathway (ThromboPath®), thromboelastometry and the levels of factor VII, VIII, and antithrombin in two groups of cirrhotic patients: Group 1 (n = 25) - patients with moderate or large esophageal or gastric varices, who had never experienced acute gastrointestinal bleeding and Group 2 (n = 24) - patients with a history of variceal bleeding. RESULTS: Despite the differences in MELD score and the results of basic laboratory tests indicating more severe cirrhosis and suggesting a greater risk of bleeding in Group 2, the results of thromboelastometry did not differ significantly between groups. The ThromboPath® test results [ThP B: 67.8 ±â€¯13.4 versus 59.09 ±â€¯12.4%, p = 0.023] and factor VII level [69.04 ±â€¯24.16 vs 53.54 ±â€¯25.06, p = 0.032] confirmed greater plasma procoagulant activity in Group 1 compared to Group 2. However, there were no statistically significant differences in thrombin generation after activation of the protein C. Plasma of patients in Group 2 was more resistant to anticoagulation with protein C compared to Group 1 (PICI%: 65.58 ±â€¯7.24 versus 55.64 ±â€¯13.07%, p = 0.001). CONCLUSION: The results of our study confirm the lack of influence of coagulation disorders on the occurrence of variceal bleeding. Moreover, the results of ThromboPath® assay indicate hypercoagulability in patients with a history of variceal bleeding and more severe liver cirrhosis, compared to patients who have never bled.

Blood platelet function abnormalities in cirrhotic patients with esophageal varices in relation to the variceal bleeding history.

Objective: The study aimed at assessing the effect of thrombocytopenia and platelet function abnormalities on the occurrence of variceal bleeding in patients with cirrhosis. Methods: The results of impedance aggregometry, von Willebrand factor antigen level and thromboelastometry (TEM) with and without the addition of a platelet inhibitor (FIBTEM®, EXTEM® test, respectively) were compared in two patient groups: Group 1 (n = 32) - patients with moderate or large esophageal or gastric varices, who had never had symptoms of acute gastrointestinal bleeding and Group 2 (n = 26) - patients with history of variceal bleeding. Results: Standard clotting test indicated more hypocoagulable profile in Group 2 compared to Group 1. However, no differences in any TEM component were observed between groups in EXTEM® test. The contribution of platelets to clot strength was significantly higher in Group 2 than in Group 1 [PLT% = 74.2 (67.5-80.4) versus 68.8 (63.7-76.5) %; p = .039]. The aggregation index was also higher in Group 2 compared to Group 1, although not statistically significant [% of healthy = 96.9 (73.2-140.1) versus 67.6 (52.5-118.8) %, p = .195]. No differences in vWF antigen levels were observed between groups. Conclusions: The results of thromboelastometry and aggregometry indicate increased contribution of platelets in clot formation in patients with a history of variceal bleeding compared to cirrhotic patients who never bled. Comparable effectiveness of hemostasis in both groups is most likely associated with the compensatory role of platelets. Increased platelet activity in this group of patients is probably due to a mechanism independent of the von Willebrand factor antigen level.

The imbalance of peripheral interleukin-18 and transforming growth factor-ß1 levels in patients with cirrhosis and esophageal varices.

INTRODUCTION: The presence of esophageal varices in liver cirrhosis indicates clinically significant portal hypertension (PH), that results from structural and dynamic changes in the liver and systemic circulation including the activation of several fibrotic and inflammatory pathways. We assessed if interleukin-18 (IL-18) and transforming growth factor-ß1 (TGF-ß1) serum levels can be used as PH markers and reflect its severity. MATERIAL AND METHODS: IL-18 and TGF-ß1 peripheral blood levels were analyzed in 83 cirrhotic patients with esophageal varices compared to healthy individuals, in relation to MELD and Child-Pugh scores, laboratory and Doppler ultrasound parameters, and non-selective beta-blocker therapy (NSBB). RESULTS: IL-18 concentration was significantly higher in cirrhotic patients, while TGF-ß1 concentration was lower than in controls. MELD score correlated positively with IL-18 levels and negatively with TGF-ß1 levels. IL-18 levels correlated positively with bilirubin, INR, ALT and AST levels, and negatively with albumin levels and erythrocyte count. TGF-ß1 levels correlated positively with platelet count, leukocyte, and erythrocyte count, and negatively with bilirubin levels and prothrombin time. Moreover, significant correlations were found: between IL and 18 levels and portal, mesenteric superior, and splenic vein velocity, and between TGF-ß1 levels and splenic vein diameter and spleen size. In a subgroup of patients, IL-18 levels significantly decreased after NSBB. CONCLUSION: The observed imbalance of peripheral IL-18 and TGF-ß1 levels indicates clinically significant PH associated with the presence of esophageal varices in cirrhosis. The correlation of IL-18 levels with liver failure indicators and decrease with NSBB suggest an important role of IL-18 in disease progression and its potential use as noninvasive test for PH assessment.

The added value of magnifying endoscopy in diagnosing patients with certain gastroesophageal reflux disease.

PURPOSE: In most cases gastroesophageal reflux disease proceeds without macroscopic erosions in the esophagus. We aimed to clarify if abnormalities detectable in magnifying endoscopy may offer additional diagnostic criteria for gastroesophageal reflux disease and to what histopathologic structures do they correspond. PATIENTS/METHODS: Esophageal mucosa above and below Z-line was evaluated under x115 magnification in 67 gastroesophageal reflux disease patients (11 with erosive reflux disease, 28 with Barrett's esophagus, 28 with nonerosive reflux disease) and in 12 patients without gastroesophageal reflux disease (negative control group). Features characteristic of gastroesophageal reflux disease were specified by comparing erosive reflux disease and Barrett's esophagus patients with negative control group. Afterwards the presence of identified features were evaluated in nonerosive reflux disease group. Interobserver agreement in the recognition of the proposed criteria was rated. Biopsies collected from the mucosa above Z-line were evaluated histologically after hematoxylin and eosin staining. RESULTS: Endoscopic lesions characteristic of gastroesophageal reflux disease were: microerosions, abnormal intrapapillary capillary loops, obscured palisade vessels, white points, big triangular indentations of Z-line and villous mucosa below Z-line. The presence of two or more of the above features indicated gastroesophageal reflux disease with 97% sensitivity and 75% specificity. Substantial interobserver agreement was achieved in evaluation of obscured palisade vessels, abnormal intrapapillary capillary loops and white points. Endoscopic lesions were correlated to histology. Lesions identified with magnifying endoscopy were helpful in discerning between negative control group and nonerosive reflux disease patients. CONCLUSIONS: Magnifying endoscopy reveals abnormalities that can be used as additional endoscopic diagnostic criteria of gastroesophageal reflux disease.

The HLA-DQß1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans.

Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQß1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQß1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10(-04), Sweden P=7.44 × 10(-05)). Combining all five European data sets - Central Europe, Italy, Spain, Poland and Sweden - the insertion is achalasia associated with Pcombined=1.67 × 10(-35). In addition, we observe that the frequency of the insertion shows a geospatial north-south gradient. The insertion is less common in northern (around 6-7% in patients and 2% in controls from Sweden and Poland) compared with southern Europeans (~16% in patients and 8% in controls from Italy) and shows a stronger attributable risk in the southern European population. Our study provides evidence that the prevalence of achalasia may differ between populations.

Endothelin 1 and transforming growth factor-ß1 correlate with liver function and portal pressure in cirrhotic patients.

OBJECTIVE: The invasive measurement of hepatic venous pressure gradient is the recommended method for the assessment of portal hypertension. We assessed if the mediators that regulate portal hypertension may be used as noninvasive markers of portal hypertension and liver insufficiency. MATERIALS AND METHODS: We explored in prospective, observational study the concentration of endothelin-1, nitric oxide, and transforming growth factor-ß1/2 in peripheral and hepatic venous blood; their relationship with the values of portal hypertension and liver insufficiency; and their level changes 4-6 months after non-selective beta-blocker therapy in cirrhotic patients with non-bleeding esophageal varices. RESULTS: (1) Cirrhotics have significantly increased peripheral endothelin 1 and decreased transforming growth factor-ß1 levels; (2) peripheral levels of all factors correlated significantly with their hepatic levels; (3) after therapy, peripheral endothelin-1 levels significantly increased, but transforming growth factor-ß2 levels decreased and were lower in patients with pressure gradient value normalization; (4) before and after therapy, peripheral and hepatic endothelin-1, transforming growth factor-ß1/2 levels correlated significantly with liver failure indicators (laboratory parameters, Child-Pough and MELD scores) and pressure gradient values. CONCLUSIONS: Peripheral endothelin-1 and transforming growth factor-ß1 levels, which strongly correlate with their hepatic levels, reflect the stage of portal hypertension and liver insufficiency in cirrhosis.

Magnification endoscopy and chromoendoscopy in evaluation of specialized intestinal metaplasia in Barrett's Esophagus.

BACKGROUND: Specialized intestinal metaplasia (SIM) in Barrett's esophagus is a risk factor of esophageal adenocarcinoma. It often occurs focally and cannot be distinguished from surrounding columnar epithelium with conventional endoscopy. AIMS: The purpose of this study was evaluation of methylene blue (MB) staining and magnification endoscopy with comparison of pit-pattern classifications according to Endo and Guelrud, in detection of SIM in Barrett's esophagus. METHODS: Twenty-five patients, aged 33-77 years (average 57 years), with displacement of Z line were prospectively enrolled and underwent gastroscopy with the use of magnification up to 115 times (Olympus GIF Q160Z). Biopsy for histopathologic examination was taken from sites stained with MB and/or places with particular pit patterns. A control group consisted of ten patients with normal gastro-esophageal junction. RESULTS: SIM was proved in nine patients, and significantly more frequently in patients with hiatal hernia and Barrett's segment longer than 3 cm. Round or thin linear pit patterns according to Guelrud's and small round and straight pit patterns according to Endo's classification were coupled with columnar epithelium. SIM was associated with deep linear and foveolar pit patterns in Guelrud's classification. Other pit patterns were less characteristic. Both classifications had high sensitivity (Endo's 85.7%, Guelrud's 92.8%) but poor specificity (respectively, 21.15 and 28.4%) in detection of SIM. Sensitivity and specificity of MB staining were, respectively, 71.4 and 40.6%. CONCLUSIONS: Despite existing association between mucosal surface structure and histology, we find no convincing data indicating that pit-pattern evaluation may replace multiple biopsies taken according to recommendations from Seattle for detection of SIM in Barrett's esophagus.

[Therapeutic management of peptic ulcer bleeding]. / Postepowanie farmakologiczne w krwawieniach w chorobie wrzodowej zoladka i dwunastnicy.

Despite development of new diagnostic and therapeutic methods bleeding from peptic ulcer is still associated with high rate of complications and mortality. Apart from endoscopic therapy, pharmacological treatment is of great importance. Affecting platelet aggregation and fibrin formation low pH level of gastric juice impairs processes of coagulation. The fastest and most stable control of acid secretion is achieved by proton pump inhibitors. In the cases of active bleeding from peptic ulcer or signs of recent bleeding such as visible vessel or adhering clot, administration of high doses of proton pump inhibitors by continuous intravenous infusion significantly reduces bleeding recurrence rate. Among patients with Helicobacter pylori (H. pylori) infection, eradication of the bacteria after bleeding episode is mandatory.