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.

Questionnaire-Based Study of 81 Patients in Poland to Evaluate the Course of Inflammatory Bowel Disease and the Effects of the COVID-19 Pandemic on Quality of Life and Mental State from February to June 2021.

BACKGROUND The COVID-19 pandemic affected many people worldwide, including those with chronic diseases. Our objective was to analyze its influence on medical care and the course of inflammatory bowel disease (IBD) in Poland. MATERIAL AND METHODS In 2021, 81 patients in Poland with IBD completed an original anonymous questionnaire about the impact of the COVID-19 pandemic on the course of their disease and mental status. The printed questionnaire was distributed to IBD patients treated at the Gastroenterology Outpatient Clinic of the University Clinical Hospital in Bialystok, and an online questionnaire was sent to patients via social media. Statistical analysis was performed using the chi-squared test, with a significance level of P<0.05. RESULTS The study group consisted of 46 women and 35 men with a mean age of 32.42 years. Fifty-nine patients had ulcerative colitis and 22 had Crohn disease. Patients reported significant deterioration in medication availability (50.62%) and restricted access to gastroenterology outpatient clinics (51.90%) (P<0.05). Of patients who contracted COVID-19, 89.47% did not require hospitalization, 32.10% (26/81) were asymptomatic, mild, or moderate, despite immunosuppressive biological treatment (27.16%, 22/81), or steroids (18.52%, 15/81). Over 50% of respondents stated the pandemic negatively affected their mental state and 30% of them associated that with worsening IBD. CONCLUSIONS During the pandemic, respondents were mainly concerned with difficulties in accessing the gastroenterology clinic and limited drug availability. The pandemic negatively affected patients' mental state. In cases of COVID-19 disease, patients with IBD were mostly asymptomatic and did not require hospitalization, despite therapy affecting the immune system.

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.

Diagnostic and therapeutic management in gastroesophageal reflux disease: consensus of the Polish Society of Gastroenterology.

The paper was prepared by an expert group appointed by the Polish Society of Gastroenterology with an aim to update and systematize the knowledge about diagnosis and treatment of gastroesophageal reflux disease (GERD). Based on the previously published guidelines of international societies, expert consensuses, and recently published good quality data, we formulated 74 statements regarding the definition, diagnosis and treatment of GERD and assessed the level of acceptance of these statements and the reliability of the data. We discussed in details the possibilities and limitations of the available diagnostic methods and therapies, with particular emphasis on the diversity of gastroesophageal reflux symptoms and complications including Barrett's esophagus. Practical principles regarding interpretation of the diagnostic tests are presented. In addition, we discussed the indications for surgical treatment as well as the situations in which surgical treatment is not indicated with emphasis on the importance of preoperative diagnostics. The role of add-on therapy and indications for maintenance treatment are defined.

Microbiome-Friend or Foe of Pancreatic Cancer?

Pancreatic ductal adenocarcinoma is one of the deadliest human neoplasms. Despite the development of new surgical and adjuvant therapies, the prognosis remains very poor, with the overall survival rate not exceeding 9%. There is now increasing evidence that the human microbiome, which is involved in many physiological functions, including the regulation of metabolic processes and the modulation of the immune system, is possibly linked to pancreatic oncogenesis. However, the exact mechanisms of action are poorly understood. Our review summarizes the current understanding of how the microbiome affects pancreatic cancer development and progression. We discuss potential pathways of microbe translocation to the pancreas, as well as the mechanism of their action. We describe the role of the microbiome as a potential marker of pancreatic cancer diagnosis, progression, and survival. Finally, we discuss the possibilities of modifying the microbiome to improve treatment effectiveness for this deadly disease.

Functional assessment of the right ventricle in patients with bronchial asthma of various severity.

INTRODUCTION: Pulmonary artery hypertension and its consequences still constitutes an underestimated clinical problem in asthma patients and its non-invasive early detection may influence proper treatment. AIM: To non-invasively examine the pulmonary artery flow parameters and right ventricular function in patients with asthma of various severity. MATERIAL AND METHODS: The analysis of parameters of echocardiography and first-pass and gated radionuclide angiography, and baseline examination in 31 patients with bronchial asthma and 16 healthy controls. RESULTS: Patients with severe asthma had higher mean pulmonary artery pressure (MPAP) compared to the healthy controls. The subgroup analysis of patients who suffered from asthma in their childhood showed that individuals with severe asthma were characterized by significantly higher MPAP than those with the mild/moderate condition (19.16 ±7.51 mm Hg vs. 5.0 ±1.15 mm Hg, p = 0.025). Gated, but not first-pass, radionuclide angiography revealed that individuals with severe asthma were characterized by a lower right ventricular ejection fraction (RVEF). Further analysis of the subgroup of patients in whom the initial manifestation of dyspnoea occurred no earlier than 6 years prior to the study showed that the RVEF of individuals with severe asthma was significantly lower compared to those with mild/moderate asthma (39.8 ±4.79% vs. 51.4 ±8.65%, p = 0.019). CONCLUSIONS: The pulmonary artery pressure in patients with severe asthma is significantly higher than in healthy individuals; in contrast, these two groups did not differ significantly in terms of the right ventricular echocardiographic characteristics. Gated radionuclide angiography, but not the first-pass technique, allowed for the detection of subtle right ventricular ejection fraction changes in asthma patients.

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.

Transgenic Expression of PRSS1R122H Sensitizes Mice to Pancreatitis.

BACKGROUND & AIMS: Mutations in the trypsinogen gene (PRSS1) cause human hereditary pancreatitis. However, it is not clear how mutant forms of PRSS1 contribute to disease development. We studied the effects of expressing mutant forms of human PRSS1 in mice. METHODS: We expressed forms of PRSS1 with and without the mutation encoding R122H (PRSS1R122H) specifically in pancreatic acinar cells under control of a full-length pancreatic elastase gene promoter. Mice that did not express these transgenes were used as controls. Mice were given injections of caerulein to induce acute pancreatitis or injections of lipopolysaccharide to induce chronic pancreatitis. Other groups of mice were fed ethanol or placed on a high-fat diet to induce pancreatitis. Pancreata were collected and analyzed by histology, immunoblots, real-time polymerase chain reaction, and immunohistochemistry. Trypsin enzymatic activity and chymotrypsin enzymatic activity were measured in pancreatic homogenates. Blood was collected and serum amylase activity was measured. RESULTS: Pancreata from mice expressing transgenes encoding PRSS1 or PRSS1R122H had focal areas of inflammation; these lesions were more prominent in mice that express PRSS1R122H. Pancreata from mice that express PRSS1 or PRSS1R122H had increased levels of heat shock protein 70 and nuclear factor (erythroid-derived 2)-like 2, and reduced levels of chymotrypsin C compared with control mice. Increased expression of PRSS1 or PRSS1R122H increased focal damage in pancreatic tissues and increased the severity of acute pancreatitis after caerulein injection. Administration of lipopolysaccharide exacerbated inflammation in mice that express PRSS1R122H compared to mice that express PRSS1 or control mice. Mice that express PRSS1R122H developed more severe pancreatitis after ethanol feeding or a high-fat diet than mice that express PRSS1 or control mice. Pancreata from mice that express PRSS1R122H had more DNA damage, apoptosis, and collagen deposition and increased trypsin activity and infiltration by inflammatory cells than mice that express PRSS1 or control mice. CONCLUSIONS: Expression of a transgene encoding PRSS1R122H in mice promoted inflammation and increased the severity of pancreatitis compared with mice that express PRSS1 or control mice. These mice might be used as a model for human hereditary pancreatitis and can be studied to determine mechanisms of induction of pancreatitis by lipopolysaccharide, ethanol, or a high-fat diet.

Oncogenic KRAS Reduces Expression of FGF21 in Acinar Cells to Promote Pancreatic Tumorigenesis in Mice on a High-Fat Diet.

BACKGROUND & AIMS: Obesity is a risk factor for pancreatic cancer. In mice, a high-fat diet (HFD) and expression of oncogenic KRAS lead to development of invasive pancreatic ductal adenocarcinoma (PDAC) by unknown mechanisms. We investigated how oncogenic KRAS regulates the expression of fibroblast growth factor 21, FGF21, a metabolic regulator that prevents obesity, and the effects of recombinant human FGF21 (rhFGF21) on pancreatic tumorigenesis. METHODS: We performed immunohistochemical analyses of FGF21 levels in human pancreatic tissue arrays, comprising 59 PDAC specimens and 45 nontumor tissues. We also studied mice with tamoxifen-inducible expression of oncogenic KRAS in acinar cells (KrasG12D/+ mice) and fElasCreERT mice (controls). KrasG12D/+ mice were placed on an HFD or regular chow diet (control) and given injections of rhFGF21 or vehicle; pancreata were collected and analyzed by histology, immunoblots, quantitative polymerase chain reaction, and immunohistochemistry. We measured markers of inflammation in the pancreas, liver, and adipose tissue. Activity of RAS was measured based on the amount of bound guanosine triphosphate. RESULTS: Pancreatic tissues of mice expressed high levels of FGF21 compared with liver tissues. FGF21 and its receptor proteins were expressed by acinar cells. Acinar cells that expressed KrasG12D/+ had significantly lower expression of Fgf21 messenger RNA compared with acinar cells from control mice, partly due to down-regulation of PPARG expression-a transcription factor that activates Fgf21 transcription. Pancreata from KrasG12D/+ mice on a control diet and given injections of rhFGF21 had reduced pancreatic inflammation, infiltration by immune cells, and acinar-to-ductal metaplasia compared with mice given injections of vehicle. HFD-fed KrasG12D/+ mice given injections of vehicle accumulated abdominal fat, developed extensive inflammation, pancreatic cysts, and high-grade pancreatic intraepithelial neoplasias (PanINs); half the mice developed PDAC with liver metastases. HFD-fed KrasG12D/+ mice given injections of rhFGF21 had reduced accumulation of abdominal fat and pancreatic triglycerides, fewer pancreatic cysts, reduced systemic and pancreatic markers of inflammation, fewer PanINs, and longer survival-only approximately 12% of the mice developed PDACs, and none of the mice had metastases. Pancreata from HFD-fed KrasG12D/+ mice given injections of rhFGF21 had lower levels of active RAS than from mice given vehicle. CONCLUSIONS: Normal acinar cells from mice and humans express high levels of FGF21. In mice, acinar expression of oncogenic KRAS significantly reduces FGF21 expression. When these mice are placed on an HFD, they develop extensive inflammation, pancreatic cysts, PanINs, and PDACs, which are reduced by injection of FGF21. FGF21 also reduces the guanosine triphosphate binding capacity of RAS. FGF21 might be used in the prevention or treatment of pancreatic cancer.

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.

Esophageal pH and impedance reflux parameters in relation to body mass index, obesity-related hormones, and bariatric procedures.

Introduction Obese patients have a higher risk of gastroesophageal reflux disease (GERD), but obesity­related hormonal changes associated with GERD and the effects of bariatric therapy on reflux are unclear. Objectives The aim of the study was to assess reflux parameters in relation to bariatric therapy and hormonal changes in obese patients. Patients and methods This prospective observational study with a 1­year follow­up included 53 obese patients undergoing bariatric therapies. Esophageal pH and impedance monitoring tests were performed and circulating hormone levels were analyzed. Results Esophageal acid exposure time (%AET) and the number of refluxes correlated positively with body mass index. There were several significant, although weak, correlations of pH and impedance parameters with ghrelin and omentin levels. Patients with abnormal %AET had lower ghrelin levels and those with abnormal reflux number had lower omentin levels than patients with normal parameters. Although we observed certain changes including increased %AET and bolus clearance time (BCT) after laparoscopic sleeve gastrectomy, a reduced BCT and number of refluxes after gastric band, and nonsignificant changes after intragastric balloon, the overall bariatric therapy did not significantly impact on the final GERD diagnosis. GERD before and after therapy was present in 42% of patients. De novo GERD developed in 17.8% of patients, while a similar percentage of patients with initial GERD had normal pH and impedance after therapy. Patients with de novo or persistent GERD had a similar percentage of weight loss as patients without GERD. Conclusions Bariatric therapy and percentage of weight loss do not significantly affect GERD. The observed hormonal changes alone do not fully explain the high prevalence of GERD in obese patients.

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.

Lipocalin-2 Promotes Pancreatic Ductal Adenocarcinoma by Regulating Inflammation in the Tumor Microenvironment.

Lipocalin-2 (LCN2) promotes malignant development in many cancer types. LCN2 is upregulated in patients with pancreatic ductal adenocarcinoma (PDAC) and in obese individuals, but whether it contributes to PDAC development is unclear. In this study, we investigated the effects of Lcn2 depletion on diet-induced obesity, inflammation, and PDAC development. Mice with acinar cell-specific expression of KrasG12D were crossed with Lcn2-depleted animals and fed isocaloric diets with varying amounts of fat content. Pancreas were collected and analyzed for inflammation, pancreatic intraepithelial neoplasia (PanIN), and PDAC. We also used a syngeneic orthotopic PDAC mouse model to study tumor growth in the presence or absence of Lcn2 expression. In addition, to understand the mechanistic role of how LCN2 could be mediating PDAC, we studied LCN2 and its specific receptor solute carrier family 22 member 17 (SLC22A17) in human pancreatic cancer stellate cells (PSC), key mediators of the PDAC stroma. Depletion of Lcn2 diminished extracellular matrix deposition, immune cell infiltration, PanIN formation, and tumor growth. Notably, it also increased survival in both obesity-driven and syngeneic orthotopic PDAC mouse models. LCN2 modulated the secretion of proinflammatory cytokines in PSC of the PDAC tumor microenvironment, whereas downregulation of LCN2-specific receptor SLC22A17 blocked these effects. Our results reveal how LCN2 acts in the tumor microenvironment links obesity, inflammation, and PDAC development. Cancer Res; 77(10); 2647-60. ©2017 AACR.

The effect of omeprazole treatment on the gut microflora and neutrophil function.

BACKGROUND AND AIM: Proton pump inhibitors (PPIs) may increase the risk of Clostridium difficile infections. There are interactions between gut microbiota and innate immune cells including neutrophils. We evaluated the effect of treatment with omeprazole on the gut microflora and neutrophil function. METHODS: In 50 patients, we evaluated the effect of 4-week omeprazole treatment (n=25 with 20mg per day and n=25 with 20mg twice daily) on intragastric pH, results of stool culture and lactulose hydrogen breath test (LHBT) and neutrophil function. RESULTS: The treatment caused significant increase of the mean intragastric pH, especially in the group with 20mg omeprazole twice daily (from 2.05±0.59 to 5.06±1.6, P<0.001). In LHBT, the increase of hydrogen concentration was observed in higher percentage of patients with 20mg of omeprazole twice daily, compared to patients with the lower dose (42.1% vs 29.4%; ns). Four weeks of omeprazole treatment have caused considerable changes in stool culture results. Patients treated with higher dose of omeprazole have had some tendency to decrease diversity of colonic microflora in comparison with patients treated with the lower dose of omeprazole. Treatment with omeprazole did not result in C. difficile positive stool culture and had no significant effect on neutrophil function. CONCLUSIONS: Omeprazole treatment have caused considerable changes in stool culture results. Patients treated with the higher dose had some tendency to decreased diversity of colonic microflora and towards changes in fermenting bacteria of the gut. The potential effect of omeprazole on gut microflora does not depend on neutrophil function deterioration.

Variation in blood levels of hormones in obese patients following weight reduction induced by endoscopic and surgical bariatric therapies.

BACKGROUND: Beneficial clinical effects of weight reduction following bariatric therapies is not fully understood and maybe related to the complex interactions between leptin, adiponectin, visfatin, omentin, and ghrelin. The aim of study was to investigate their timeline changes associated with weight reduction and their profile in relation to the type of treatment and its efficacy. METHODS: Circulating hormones levels were analyzed before and after endoscopic and surgical procedures in 67 obese patients and compared to non-obese healthy controls. RESULTS: Obese patients had higher leptin levels and lower levels of adiponectin, visfatin, omentin, and ghrelin than non-obese controls. During the consecutive follow-up visits after treatment, there was a gradual decrease in leptin levels and an increase in adiponectin levels to the levels observed in non-obese. At 50-54weeks, the ghrelin levels were lower and the levels of adiponectin and visfatin, but not omentin, were higher compared to their baseline values. BMI correlated with ghrelin and leptin levels. The percentage of total weight loss correlated positively with adiponectin levels and negatively with leptin levels. Patients with adequate weight loss had a significantly lower leptin concentration than those with treatment failure. There were timeline variations in hormone levels between endoscopic and bariatric therapies, however there were no significant differences in the median their concentration at 50-54weeks after therapy. CONCLUSION: Our study supports observations that weight loss itself, rather than the procedure type, is responsible for hormonal variation. The leptin levels reflect the best the body weight changes after bariatric therapies.

Buried bumper syndrome: a rare complication of percutaneous endoscopic gastrostomy.

Feeding via percutaneous endoscopic gastrostomy (PEG) is the preferred form of alimentation when oral feeding is impossible. Although it is a relatively safe method, some complications may occur. One uncommon PEG complication is buried bumper syndrome. In this paper we report a case of buried bumper syndrome, successfully managed with PEG tube repositioning.