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Background: Functional gastrointestinal disorders (FGIDs), now known as disorders of gut-brain interaction (DGBIs), such as Irritable Bowel Syndrome (IBS) and Functional Dyspepsia (FD), significantly impact global health, reducing quality of life and burdening healthcare systems. This study addresses the epidemiological gap in Poland, focusing on the West Pomeranian Voivodeship., Methods: We conducted a cross-sectional study of 2070 Caucasian patients (58.2% female, mean age 57.5 ± 15.1 years) undergoing gastrointestinal endoscopic examinations at Pomeranian Medical University from 2021 to 2023. Data were collected using Rome IV diagnostic questionnaires and correlated with gastroduodenoscopy and colonoscopy findings. Exclusion criteria were age under 18, pregnancy, Crohn's disease, ulcerative colitis, severe comorbidities, cancer, immunosuppressive therapy, ileostomy/colostomy, incomplete questionnaires, or lack of consent., Results: Using Rome IV criteria, IBS was diagnosed in 436 participants (21.1%) and FD in 248 participants (12.0%). Post-endoscopic evaluation revised FD diagnoses to 184 individuals (8.9%). Females had a higher prevalence of IBS and FD (OR 1.64 and 1.61, respectively). No significant association was found between higher BMI and increased risk of IBS and FD. Hypertension and diabetes prevalence were 35.1% and 13.0%, respectively. Individuals with a history of COVID-19 had a higher risk of developing IBS (OR 1.47, P = 0.050)., Conclusions: Our study provides crucial epidemiological data on IBS and FD in Poland, emphasizing the importance of endoscopic evaluations. Our findings highlight the need for regional studies to understand local DGBI prevalence, aiding targeted healthcare strategies., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the ethics committee of the Pomeranian Medical University in Szczecin (resolution no KB-0012/197/19) and all participants gave written informed consent to participate. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background/objectives: Crohn's disease is known for being associated with an abnormal composition of the bacterial flora, dysbiosis and intestinal function disorders. Metabolites produced by gut microbiota play a pivotal role in the pathogenesis of CD, and the presence of unspecific extraintestinal manifestations., Methods: The aim of this study was a determination of the level of bacterial metabolites in blood plasma in patients with Crohn's disease. CD patients (29) and healthy individuals (30) were recruited for this study. Bacterial metabolites (SCFAs and TMAO panel) were measured by a liquid chromatography-mass spectrometry system., Results: A significant correlation ( p -value < 0.05) between CD and bacterial metabolites was obtained for three of eight tested SCFAs; acetic acid (reduced in CD; FC 1.7; AUC = 0.714), butyric acid (increased; FC 0.68; AUC = 0.717), 2MeBA (FC 1.168; AUC = 0.702), and indoxyl (FC 0.624). The concentration of CA (FC 0.82) and choline (FC 0.78) in plasma was significantly disturbed according to the biological treatment. Choline level (FC 1.28) was also significantly disturbed in the patients treated with glucocorticoids. In total, 68.97% of Crohn's patients presented extraintestinal manifestations (EIMs) of Crohn's disease, mainly osteoarticular complications. The level of BA was statistically significantly elevated in patients with extraintestinal (FC 0.602) manifestations, while in the group of patients with osteoarticular complications, a significant difference in the level of betaine (FC 1.647) was observed., Conclusions: The analyzed bacterial metabolites of plasma may significantly help in the diagnostic process, and in the monitoring of the disease course and treatment, in a lowly invasive way, as biomarkers after additional research on a larger group of patients.

Hypercholesterolemia-associated oxidative stress increases the formation of oxidized low-density lipoprotein (oxLDL), which can affect endothelial cell function and potentially contribute to renal dysfunction, as reflected by changes in urinary protein excretion. This study aimed to investigate the impact of exogenous oxLDL on urinary excretion of albumin and nephrin. LDL was isolated from a patient with familial hypercholesterolemia (FH) undergoing lipoprotein apheresis (LA) and was oxidized in vitro with Cu (II) ions. Biochemical markers of LDL oxidation, such as TBARS, conjugated dienes, and free ε-amino groups, were measured. Wistar rats were treated with a single intraperitoneal injection of PBS, LDL, or oxLDL (4 mg of protein/kg b.w.). Urine was collected one day before and two days after the injection. We measured blood lipid profiles, urinary protein excretion (specifically albumin and nephrin), and markers of systemic oxidative stress (8-OHdG and 8-iso-PGF2α). The results showed that injection of oxLDL increased urinary albumin excretion by approximately 28% (310 ± 27 μg/24 h vs. 396 ± 26 μg/24 h, p = 0.0003) but had no effect on nephrin excretion. Neither PBS nor LDL had any effect on urinary albumin or nephrin excretion. Additionally, oxLDL did not affect systemic oxidative stress. In conclusion, hypercholesterolemia may adversely affect renal function through oxidatively modified LDL, which interferes with the renal handling of albumin and leads to the development of albuminuria.

Background: Pancreatic cancer is the most common pancreatic solid malignancy with an aggressive clinical course and low survival rate. There are a limited number of reliable prognostic biomarkers and a need to understand the pathogenesis of pancreatic tumors; neuroendocrine (PNET) and pancreatic ductal adenocarcinomas (PDAC) encouraged us to analyze the serum metabolome of pancreatic tumors and disturbances in the metabolism of PDAC and PNET., Methods: Using the AbsoluteIDQ ® p180 kit (Biocrates Life Sciences AG, Innsbruck, Austria) with liquid chromatography-mass spectrometry (LC-MS), we identified changes in metabolite profiles and disrupted metabolic pathways serum of NET and PDAC patients., Results: The concentration of six metabolites showed statistically significant differences between the control group and PDAC patients ( p.adj < 0.05). Glutamine (Gln), acetylcarnitine (C2), and citrulline (Cit) presented a lower concentration in the serum of PDAC patients, while phosphatidylcholine aa C32:0 (PC aa C32:0), sphingomyelin C26:1 (SM C26:1), and glutamic acid (Glu) achieved higher concentrations compared to serum samples from healthy individuals. Five of the tested metabolites: C2 (FC = 8.67), and serotonin (FC = 2.68) reached higher concentration values in the PNET serum samples compared to PDAC, while phosphatidylcholine aa C34:1 (PC aa C34:1) (FC = -1.46 (0.68)) had a higher concentration in the PDAC samples. The area under the curves (AUC) of the receiver operating characteristic (ROC) curves presented diagnostic power to discriminate pancreatic tumor patients, which were highest for acylcarnitines: C2 with AUC = 0.93, serotonin with AUC = 0.85, and PC aa C34:1 with AUC = 0.86., Conclusions: The observations presented provide better insight into the metabolism of pancreatic tumors, and improve the diagnosis and classification of tumors. Serum-circulating metabolites can be easily monitored without invasive procedures and show the present clinical patients' condition, helping with pharmacological treatment or dietary strategies.

Objectives: Rectal neuroendocrine tumors (rNETs) are potentially malignant lesions. In our study, we aimed to retrospectively check whether the rectal neuroendocrine tumors were found in colonoscopy examinations carried out as a part of Polish colonoscopy screening program (PCSP)., Materials and Methods: We retrospectively analyzed the colonoscopy and histopathological database of examinations conducted as a part of PCSP in our institution in the years 2005-2021. We also checked the method by which the tumor was removed, its characteristics based on photo documentations and followed up the patients., Results: The 10568 colonoscopy examinations were performed in PCSP in the years 2005-2021. Seven patients with a mean age of 53 with rNETs (1 in every 1510 colonoscopy) were detected. The polyp mean size was 5 mm. All the lesions were well differentiated tumors. First half of the colonoscopy examinations was performed in the years 2005-2012 and in that time three rNETs were detected, four rNETs were detected in the years 2012-2021. Even despite their typical appearance the neuroendocrine origin was not suspected in majority of cases and all tumors, except one, were removed with improper method. One of the patients underwent transanal endoscopic microsurgery of the scar. All patients are disease free in median follow-up of 108 months., Conclusion: Rectal NETs are detected in the screening colonoscopy program. In majority of cases, they are not suspected by endoscopists on colonoscopy, but diagnosed after removal in histopathological examinations. There is a need of education of endoscopists in recognition and methods of treatment of rNETs.

Crohn's disease (CD) may affect the entire gastrointestinal tract including its upper part. However, this aspect is poorly addressed in scientific literature and considered a rare finding. Here we aimed to prospectively investigate the prevalence, characteristics and clinical significance of upper gastrointestinal tract involvement in patients with CD, with particular focus on stomach bamboo joint-like appearance (BJA), Helicobacter pylori status and presence of microscopic changes. 375 prospectively recruited patients were included. In CD patients the prevalence of gastric and duodenal, but not esophageal, mucosal lesions, such as gastric mucosal inflammation, duodenal edema, ulcerations, and duodenal bulb deformation was significantly higher (at least p < 0.01 for all). Similar results were found when only H. pylori negative individuals were analyzed. Moreover, BJA of the stomach and in case of H. pylori negative patients also duodenal bulb deformation were detected exclusively in CD patients. Presence of BJA lesion was not significantly associated with neither duration of the disease nor use/history of biologic treatment. Despite absence of H. pylori infection microscopic features of chronic gastritis were found in almost all (93.5%) patients, and in 31% of controls (p < 0.00001). Our analysis outlines that upper gastrointestinal tract involvement in CD is a very common event and frequently manifests with a highly specific BJA lesion. Furthermore, our study reveals that in almost all CD patients features of H. pylori negative gastritis are present., (© 2023. The Author(s).)

Non-functioning pancreatic neuroendocrine tumours (NF-pNETs) are potentially malignant neoplasms that are detected with increasing frequency. The management of small (≤ 2 cm) asymptomatic NF-pNETs remains an area of controversy and clinical dilemma. Follow-up seems to be a reasonable strategy because of the relatively limited metastatic potential of these tumours, the good clinical prognosis, and considering the high complication rate associated with surgery. However, some studies show metastatic potential of these tumours, fuelling an ongoing debate in the literature regarding their management. Making the decision to observe or perform surgery is thus not an easy task. New, promising therapeutic methods involving ablation under endoscopic ultrasound (EUS) guidance with ethanol or radiofrequency ablation have been applied for these lesions with good clinical outcomes but only with short-term follow-up data. In this review, we address the emerging question of when to follow-up and when to perform surgery for small asymptomatic pancreatic tumours, with consideration of the potential of ablative therapies.

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. It is characterized by a chronic course with periods of aggravations and remissions. Among patients, 25-55% present with ulcerative proctitis (UP) at the time of diagnosis. UP is well-treated disease associated with a good prognosis. UP is characterized by a less aggressive course than the left-sided form of UC and pancolitis, with a good response to topical treatment. Moreover, UP is associated with a lower risk of severe aggravations and systemic and local complications and lower need for colectomy, hospitalization and glucocorticosteroids and immunosuppressive drugs, in comparison with more extensive forms of the disease. Thus, the key issue is to prognose the natural course of the disease in order to identify high-risk patients and apply biological or immunosuppressive treatment early to prevent the development of complications. In this review, we summarize the current knowledge about the natural course of UP and discuss risks and protective factors related to disease progression and current treatment concepts.

A growing number of studies indicate the potential involvement of various populations of bone marrow-derived stem cells (BMSCs) in tissue repair. However, the mobilization of BMSCs to the peripheral blood (PB) in acute and chronic pancreatitis (AP and CP) has not been investigated. A total of 78 patients were assigned into AP, CP, and healthy control groups in this study. Using flow cytometry, we found that VSELs, EPCs, and CD133 + SCs were mobilized to the PB of patients with both AP and CP. Interestingly, AP and CP patients exhibited lower absolute number of circulating MSCs in the PB compared to healthy individuals. SC mobilization to the PB was more evident in patients with AP than CP and in patients with moderate/severe AP than mild AP. Using ELISA, we found a significantly increased HGF concentration in the PB of patients with AP and SDF1 α in the PB of patients with CP. We noted a significant positive correlation between SDF1 α concentration and the mobilized population of CD133 + SCs in AP and between C5a and the mobilized population of VSELs moderate/severe AP. Thus, bone marrow-derived SCs may play a role in the regeneration of pancreatic tissue in both AP and CP, and mobilization of VSELs to the PB depends on the severity of AP., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Krzysztof Dąbkowski et al.)

The gastric microbiota in Crohn's disease (CD) has not been studied. The purpose of the study was to evaluate differences of stomach microbiota between CD patients and controls. DNA was extracted from gastric mucosal and fluid samples, from 24 CD patients and 19 controls. 16S rRNA gene sequencing identified 1511 operational taxonomic units (OTUs), of which 239 passed the low abundance and low variance filters. All but one CD patients were HP negative. Fifteen bacterial phyla were identified in at least one mucosal or fluid site. Of these, Bacteroidota and Firmicutes accounted for 70% of all phyla. Proteobacteria, Actinobacteriota, and Fusobacteriota combined accounted for 27%. There was significant difference in the relative abundance of Bacteroidota, Proteobacteria, Fusobacteriota, and Campilobacterota between CD patients and controls only in gastric corpus samples. In gastric liquid, there was a significant difference only in Actinobacteriota. Pairwise comparison identified 67 differentially abundant OTUs in at least one site. Of these, 13 were present in more than one comparison, and four differentiating OTUs (Neisseriaceae, Neisseria, Absconditabacteriales, and Microbacteriaceae) were identified at all tested sites. The results reveal significant changes in gastric microbial profiles (beta diversity, phylum, and individual taxa levels) between H. pylori-negative CD patients and controls., (© 2021. The Author(s).)

Hypercholesterolemia and oxidative stress may lead to disturbances in the renal microvasculature in response to vasoactive agents, including P2 receptors (P2R) agonists. We investigated the renal microvascular response to diadenosine tetraphosphate (Ap 4 A), an agonist of P2R, in diet-induced hypercholesteremic rats over 28 days, supplemented in the last 10 days with tempol (2 mM) or DL-buthionine-(S,R)-sulfoximine (BSO, 20 mM) in the drinking water. Using laser Doppler flowmetry, renal blood perfusion in the cortex and medulla (CBP, MBP) was measured during the infusion of Ap 4 A. This induced a biphasic response in the CBP: a phase of rapid decrease was followed by one of rapid increase extended for 30 min in both the normocholesterolemic and hypercholesterolemic rats. The phase of decreased CBP was not affected by tempol or BSO in either group. Early and extended increases in CBP were prevented by tempol in the hypercholesterolemia rats, while, in the normocholesterolemic rats, only the extended increase in CBP was affected by tempol; BSO prevented extended increase in CBP in normocholesterolemic rats. MBP response is not affected by hypercholesterolemia. The hypercholesterolemic rats were characterized by increased urinary albumin and 8-isoPGF 2α excretion. Moreover, BSO increased the urinary excretion of nephrin in the hypercholesterolemic rats but, similar to tempol, did not affect the excretion of albumin in their urine. The results suggest the important role of redox balance in the extracellular nucleotide regulation of the renal vasculature and glomerular injury in hypercholesterolemia., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Vascular endothelial growth factor A (VEGF-A) and P2-receptors (P2Rs) are involved in the pathogenesis of diabetic nephropathy. The processing of VEGF-A by matrix metalloproteinases (MMP) regulates its bioavailability. Since the ATP-induced release of MMP-9 is mediated by P2Rs, we investigated the effect of suramin on VEGF-A excretion in urine and the urinary activity of total MMP and MMP-9., Methods: The effect of suramin (10 mg/kg, ip) on VEGF-A concentration in serum and its excretion in urine was investigated in streptozotocin (STZ)-induced diabetic rats over a 21-day period. The rats received suramin 7 and 14 days after a single STZ injection (65 mg/kg, ip). A 24-h collection of urine was performed on the day preceding the administration of STZ and the first administration of suramin and on the day before the end of the experiment. The VEGF-A in serum and urine, albumin in urine, and total activity of MMP and MMP-9 in urine were measured using immunoassays., Results: Diabetic rats are characterized by a sixfold higher urinary excretion of VEGF-A. Suramin potentiates VEGF-A urinary excretion by 36% (p = 0.046) in non-diabetic and by 75% (p = 0.0322) in diabetic rats but it did not affect VEGF-A concentration in the serum of non-diabetic and diabetic rats. Urinary albumin excretion as well as total MMP and MMP-9 activity was increased in diabetic rats, but these parameters were not affected by suramin., Conclusion: Suramin increases the urinary excretion of VEGF-A in normoglycemia and hyperglycaemia, possibly without the involvement of MMP-9. Suramin may be used as a pharmacological tool enhancing VEGF-A urinary secretion.

Introduction: Rectal neuroendocrine neoplasms (rNENs) are potentially metastatic lesions. False endoscopic diagnosis and subsequent treatment may lead to nonradical resection and metastases., Objectives: This study aimed to analyze the clinical characteristics of rNENs, investigate whether the lesion origin was suspected by endoscopists during examination and if those lesions were subsequently removed using the appropriate method, and assess the outcomes of patients after curative and noncurative resections., Patients and Methods: We analyzed the records of patients hospitalized in our department (2006-2019) with a diagnosis of rNENs. We included 40 patients with rNENs, evaluated their clinical characteristics, and investigated whether the neuroendocrine origin of the lesions was suspected on endoscopy. We compared the outcomes of patients treated with the proper method (endoscopic submucosal dissection / endoscopic mucosal resection [ESD / EMR]) and those treated with polypectomy., Results: Abnormalities appeared as typical, yellowish subepithelial lesions (n = 24), lesions resembling hyperplastic polyps (n = 12), or tumors with central depression (n = 4). The median size was 5.5 mm and most of them were G1 lesions (n = 36). Only 14 of them were suspected to be of neuroendocrine origin at the first endoscopic examination, and 12 were removed by ESD / EMR. The remaining tumors (n = 26) were removed using polypectomy. Most of the patients were disease‑free at follow‑up, but 2 patients after polypectomy and a single patient after nonradical ESD developed metastases., Conclusion: In most cases, the origin of the lesion was not suspected on colonoscopy and subsequently the tumor was removed using an inappropriate method. Endoscopists do not follow the guidelines when dealing with patients with rNENs and more emphasis should be placed on education on the management of rNENs.

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Background: Oxidative stress and dyslipidemia play a critical role in the development of cardiovascular disease (CVD). Regular intake of polyphenol-rich diets is associated with a reduced risk of CVDs., Methods: The present study was a pilot study with 24 healthy volunteers and was designed to determine if a 12-week administration of Cistus incanus herbal tea, containing phenolic acids and flavonoids, reduces cardiovascular risk factors including oxidative stress and dyslipidemia in healthy adults. Phenolic compounds profile and antibacterial activity of Cistus incanus infusion were also measured., Results: Herbal infusion led to improvement in lipid profile by increase (D4%, p = 0.033) high-density lipoprotein cholesterol concentration and decrease triglyceride (D14%, p = 0.013) concentrations. In addition, the Cistus incanus diet was associated with decreased serum concentrations of malondialdehyde (D16%, p < 0.01) and advanced oxidation protein products (D18%, p < 0.001)., Conclusions: Cistus incanus administration decreases cardiovascular risk factors including oxidative stress and dyslipidemia and this action supports the idea of using Cistus incanus tea on a daily basis as an effective dietary component for prevention of atherosclerotic CVD.

Diabetes through adenosine A1 receptor (A1R) and P2 receptors (P2Rs) may lead to disturbances in renal microvasculature. We investigated the renal microvascular response to Ap4A, an agonist of P2Rs, in streptozotocin-induced diabetic rats. Using laser Doppler flowmetry, renal blood perfusion (RBP) was measured during infusion of Ap4A alone or in the presence of A1R antagonist, either DPCPX (8-cyclopentyl-1,3-dipropylxanthine) or 8-cyclopentyltheophylline (CPT). Ap4A induced a biphasic response in RBP: a phase of rapid decrease was followed by a rapid increase, which was transient in diabetic rats but extended for 30 min in nondiabetic rats. Phase of decreased RBP was not affected by DPCPX or CPT in either group. Early and extended increases in RBP were prevented by DPCPX and CPT in nondiabetic rats, while in diabetic rats, the early increase in RBP was not affected by these antagonists. A1R mRNA and protein levels were increased in isolated glomeruli of diabetic rats, but no changes were detected in P2Y1R and P2Y2R mRNA. Presence of unblocked A1R is a prerequisite for the P2R-mediated relaxing effect of Ap4A in nondiabetic conditions, but influence of A1R on P2R-mediated renal vasorelaxation is abolished under diabetic conditions., (© 2020 S. Karger AG, Basel.)

Rectal neuroendocrine tumours are subepithelial lesions that are potentially malignant. Although the biology of these lesions has become increasingly understood and their management has been established, the endoscopic management of these tumours remains controversial. Recent studies demonstrated that compliance with guidelines is poor, and the majority of rectal neuroendocrine tumours are removed by an improper method, making management more complex and putting patients at risk of metastatic spread. Thus, there is a need to educate physicians who care for patients with these disorders. Our review has some tips and pointers for preventing mistakes in primary treatment and salvage therapy after polypectomy.

Crohn's disease is an inflammatory disorder that can affect the entire gastrointestinal tract but typically involves the ileocecal region. Before endoscopy was widely used, involvement of the esophagus, stomach, and duodenum was thought to be rare. Recent publications demonstrated that not only are upper gastrointestinal lesions common in Crohn's disease (affecting up to 75% of the patients), but they also present characteristic endoscopic findings with potential clinical significance. It was suggested that lesions in the stomach with a bamboo joint-like appearance might be an endoscopic biomarker for Crohn's disease. It was also found that this occurrence is related to a more severe disease course. Our review summarizes the literature, as well as our own observations and considerations, concerning the issue of upper gastrointestinal involvement in Crohn's disease and its clinical meaning.

In chronic kidney disease (CKD), the level of high-density lipoprotein (HDL) decreases markedly, but there is no strong inverse relationship between HDL-cholesterol (HDL-C) and cardiovascular diseases. This indicates that not only the HDL-C level, but also the other quantitative changes in the HDL particles can influence the protective functionality of these particles, and can play a key role in the increase of cardiovascular risk in CKD patients. The aim of the present study was the evaluation of the parameters that may give additional information about the HDL particles in the course of progressing CKD. For this purpose, we analyzed the concentrations of HDL containing apolipoprotein A-I without apolipoprotein A-II (LpA-I), preβ1-HDL, and myeloperoxidase (MPO), and the activity of paraoxonase-1 (PON-1) in 68 patients at various stages of CKD. The concentration of HDL cholesterol, MPO, PON-1, and lecithin-cholesterol acyltransferase (LCAT) activity were similar in all of the analyzed stages of CKD. We did not notice significant changes in the LpA-I concentrations in the following stages of CKD (3a CKD stage: 57 ± 19; 3b CKD stage: 54 ± 15; 4 CKD stage: 52 ± 14; p = 0.49). We found, however, that the preβ1-HDL concentration and preβ1-HDL/LpA-I ratio increased along with the progress of CKD, and were inversely correlated with the estimated glomerular filtration rate (eGFR), even after adjusting for age, gender, triacylglycerols (TAG), HDL cholesterol, and statin therapy (β = -0.41, p < 0.001; β = -0.33, p = 0.001, respectively). Our results support the earlier hypothesis that kidney disease leads to the modification of HDL particles, and show that the preβ1-HDL concentration is significantly elevated in non-dialyzed patients with advanced stages of CKD.

Background/aims: Hypertriglyceridaemia (HTG) and reduction and dysfunction of high density lipoprotein (HDL) are common lipid disturbances in chronic kidney disease (CKD). HTG in CKD is caused mainly by the decreased efficiency of lipoprotein lipase (LPL)-mediated very low density lipoprotein triglyceride (VLDL-TG) lipolysis. It has not been clarified whether HDL dysfunction in CKD contributes directly to HTG development; thus, the aim of this study was to assess the impact of CKD progression on the ability of HDL to enhance LPL-mediated VLDL-TG lipolysis efficiency., Methods: VLDL was isolated from non-dialysis patients in CKD stages 3 and 4 and from non-CKD patients. The VLDL was incubated with LPL at the constant LPL:VLDL-TG ratio, in the absence or presence of HDL. After incubation, the VLDL was separated and the percentage (%) of hydrolyzed TG was calculated., Results: HDL presence increased the lipolysis efficiency of VLDL isolated from CKD and non-CKD patients, for the VLDL-TG> 50 mg/dl. Its effect was dependent on the VLDL-TG and HDL-cholesterol concentrations in the reaction mixtures: the higher the concentrations of VLDL-TG and HDL-cholesterol, the greater the effect. The positive impact of HDL on VLDL lipolysis was modified by CKD progression: the percentage of lipolyzed VLDL-TG in the presence of HDL decreased with a reduction in eGFR (r=0.43, p=0.009), and for patients with stage 4 CKD, no positive impact of HDL on lipolysis was observed. The percentage of lipolyzed TG correlated negatively with apoE and apoCs content in VLDL, and positively with HDL-apoCII, as well as with VLDL and HDL apoCII/ apoCIII ratios. The progression of CKD was associated with unfavourable changes in VLDL and HDL composition; apoE and apoCs levels increased in VLDL with a decrease in eGFR whereas the HDL-cholesterol level decreased., Conclusion: The progression of CKD affects lipoprotein composition and properties, and modulates the positive impact of HDL on VLDL lipolysis efficiency. In CKD patients, HDL deficiency and dysfunction can directly affect hypertriglyceridaemia development., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Cystic pancreatic tumors are detected with increasing frequency and remain a clinical problem. Since they have different potential of malignancy the management and decision making process is a hard task. Guidelines, concerning pancreatic cystic tumors indicate the management with mucinous, serous cystic pancreatic neoplasms and solid pseudopappilary tumor, while the management with pancreatic cystic neuroendocrine tumors is not included into these standards. This review tries to answer the question are the cystic pancreatic neuroendocrine tumors different entity from solid tumors of neuroendocrine origin.The management and differential diagnosis of these neoplasms with special focus on features on imaging studies allowing preoperative diagnosis are discussed.

Background: High density lipoproteins (HDL) can be divided into two metabolically distinct fractions, one containing apolipoprotein (Apo) A-I but not ApoA-II [apolipoprotein A-I; lipoprotein (Lp) A-I] and the other containing both ApoA-I and ApoA-II (LpA-I/A-II). LpA-I fraction which, seeming to be more cardioprotective than LpA-I/A-II particles, is itself heterogeneous. Preβ1-HDL is a minor subfraction of LpA-I and the initial acceptor of cellular cholesterol in the process of reverse cholesterol transport. The aim of the study was to determine the usefulness of the determination of LpA-I fractions as indicators for the atherosclerotic process., Methods: The study included 112 patients with angiographically-documented coronary artery disease (CAD+) and 51 patients with negative results of coronary angiography (CAD-). We evaluated LpA-I concentration in serum in HDL 2 and HDL 3 fractions as well as Preβ1-HDL concentration. Furthermore, we analyzed the association of the assessed parameters with the extent and severity of CAD assessed by Gensini score., Results: CAD+ patients were characterized by a lower concentration of serum LpA-I by 19%, LpA-I in HDL 2 by 26%, higher level of Preβ1-HDL by 27%, and elevated Preβ1-HDL/LpA-I values by 62%. Univariate correlation analysis indicated that serum LpA-I and HDL-cholesterol concentrations were negatively correlated with Gensini score (R=-0.279; p=0.002, R=-0.227; p=0.016, respectively) whereas Preβ1-HDL/LpA-I values were positively correlated with the severity of CAD (R=0.529; p<0.001). In multiple linear regression, after adjusting for age, gender, preexisting hypertension, diabetes, and statin therapy, only the Preβ1-HDL/LpA-I values remained an independent determinant of atherosclerosis severity (β=-0.499; p<0.001)., Conclusions: Our results show a lower level of LpA-I and higher concentration of Preβ1-HDL in the CAD+ patients compared to the CAD- group. We suggest that the distribution of LpA-I is different in CAD and the Preβ1-HDL/LpA-I ratio may have additional value in assessing anti-atherogenic potential of HDL particles and it is likely to become a clinically valuable indicator of atherosclerosis development., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Mediastinal pseudocysts are a rare complication of acute pancreatitis. Lack of uniform treatment standards makes the management of this condition a clinical challenge. We report the case of a 43-year-old patient who presented with a left pleural effusion. Pleural fluid revealed a high amylase concentration consistent with a pancreaticopleural fistula. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a disruption of the pancreatic duct with free outflow of contrast medium into the thoracic cavity. A pancreatic stent was placed. The second day after the ERCP, the patient developed septic shock and was admitted to the intensive care unit. Computed tomography (CT) revealed mediastinal pseudocysts and bilateral pleural effusions. After bilateral drainage of the pleural cavities, the patient improved clinically, and a follow-up CT scan showed that the fluid collection and pseudocysts had resolved. We discuss the optimal strategies for diagnosing and treating patients with pancreatic thoracic pseudocysts and fistulas, as well as review the management of these conditions., Competing Interests: The authors have no financial conflicts of interest.

Introduction: EUS-guided ethanol ablation of insulinoma is a new method of treatment of this neuroendocrine tumour. Ablation is recommended in patients who are poor surgical candidates or refuse surgery. We present a case of an 81-year-old female with symptomatic insulinoma, treated successfully with EUS-guided alcoholic ablation, along with a literature review including 28 other previously described cases. The effectiveness, safety of the therapy, and technical procedure-related issues are summarised. To the best of our knowledge, this is the first described case of successful insulinoma EUS-guided ablation in Poland., Material and Methods: We searched the PubMed/Medline database to identify cases of EUS-guided alcoholic ablation. Our analysis included 14 articles (case reports or case series), with a total of 27 patients and 31 tumours described, published before February 2017., Results: The described tumours were relatively small (mean 13 mm), and the most common location was pancreatic head. The mean ethanol volume injected to the tumour was 1.8 ml and the concentration of infused alcohol varied from 95% to 98%.Side effects were observed in six cases; apart from one, they were mild and self-limiting. There was only one severe adverse event, treated conservatively with success. The median follow-up was 14.4 months (2-55 months). In all described cases ablation led to improvement of the symptoms and normalisation of glycaemia., Conclusions: The EUS-guided alcoholic ablation of insulinoma is a safe and effective method of treatment in patients who are poor surgical candidates and/or refuse surgery. The adverse effects are rare and mild and were observed when the volume of injected ethanol was equal to or above 3.0 ml. However, the data is limited, the follow-up is relatively short, and prospective studies are needed to confirm the long-term effects of treatment. The study shows also that there are important procedural differences (concentration and volume of alcohol, needle gauge, number of sessions) between the endoscopists, which should be specified.

Pancreatic cancer remains one of the deadliest solid tumors in humans and an unsolved problem of today's medicine. Experimental studies reveal that the heterogeneous and complex pancreatic cancer microenvironment is responsible, not only for cancer growth, spread, development of metastases, but also for cancer recurrence and chemotherapy resistance. Chemotherapy affecting the cancer stroma is still under clinical and experimental research and remains hope for cure of pancreatic cancer. We present the cancer microenvironment characteristics and summary of experimental studies with use of agents affecting pancreatic cancer stroma.

Lipoprotein lipase (LPL)-mediated triacylglycerol (TAG) hydrolysis in very low density lipoprotein (VLDL) is accompanied by the release of surface material containing phospholipids (PL), free cholesterol (FC) and apolipoproteins, E (apoE) and Cs (apoCII, apoCIII). The released molecules are accepted by high density lipoprotein (HDL), and new HDL-sized apoE-containing particles are also generated. A decrease in the number of HDL particles or abnormalities in their structure is associated with unfavourable changes in the features of VLDL remnants. Phosphatidylcholine liposomes (PC-L) can also act as acceptors of surface material components released from lipoproteins. Thus, the aim of this study was to assess the impact of liposomes on compositional changes of VLDL during its LPL-mediated lipolysis. VLDL isolated from human sera was incubated with LPL (LPL:VLDLTAG; 24 μg/ml:90 mg/dl) and/or PC-L (VLDLPL:PC-LPL; 1:30 weight ratio). After incubation (2h, 37 °C) VLDL was separated from other reaction products, and VLDL lipid and apolipoprotein content were analysed. Newly generated HDL-sized apoE-containing lipoproteins were separated by two-dimensional non-denaturing gradient gel electrophoresis (2D-PAGGE). The reaction of VLDL with PC-L in the presence or absence of LPL significantly affected the VLDL composition. The ratio of core (TAG+cholesteryl ester) to surface (PL+FC) lipids in VLDL decreased 1.8-fold with PC-L, 1.2-fold with LPL and 3-fold with PC-L+LPL. The reaction with PC-L and PC-L+LPL caused a 3.7-fold and 3.2-fold decrease of apoCs/apoE average weight ratio, respectively. Compositional changes in VLDL under the influence of PC-L were accompanied by an increase in the efficiency of VLDL lipolysis and the generation of apoE-containing HDL-sized particles, heterogeneous in size (from ∼ 9 to ∼ 18.8 nm) and mobility (γ and preβ). We conclude that PL-rich particles, similarly to HDL, promote the release of surface material components from VLDL during LPL-mediated lipolysis and positively influence VLDL features which can facilitate VLDL metabolism. Such PC-L activity may impact on its antiatherogenic properties., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The aim of the study was to investigate the effect of a vegan diet on the serum lipid profile with particular regard to the parameters characterizing the high-density lipoprotein (HDL) fractions in subjects without subclinical atherosclerosis, measured by carotid Doppler ultrasonography., Methods and Results: Forty-two 23 to 38 year old subjects (21 omnivores and 21 vegans) participated in the study. Compared to the omnivores, the vegan subjects were characterized by lower parameters of lipid profile: total cholesterol (p < 0.001), low-density lipoprotein (LDL)-cholesterol (p < 0.001), non-HDL-cholesterol (p < 0.001), apolipoprotein B (apoB) (p < 0.001) and phospholipids (p < 0.01). Concentration of HDL-cholesterol was apparently similar between groups. Furthermore, the parameters which characterize HDL particles (con-centration of apolipoproteins AI [apoAI] and AII, HDL-phospholipids, LpAI fraction and pre-b1-HDL fraction) were not significantly different between omnivore and vegan subjects. The apoB/apoAI ratio in vegans was lower than in omnivores (p < 0.01). There was no difference between serum concentration of triacylglycerols between omnivores and vegans. The activity of paraoxonase-1 and 8-iso-prostaglandin F2a concentration were also not different between the study groups., Conclusions: We suggest that a vegan diet may have a beneficial effect on serum lipid profile and cardiovascular protection, but it is not associated with changes in HDL composition.

The aim of the study was to estimate association of the extent of angiographically proven coronary artery disease (CAD) with plasma 8-isoprostane F2 (8-iso-PGF2α) levels as a reliable marker of lipid peroxidation and serum activity of paraoxonase-1, which demonstrates the ability to protect against lipid oxidation. The study included 105 patients with angiographically documented CAD (CAD+) and 45 patients with negative results of coronary angiography (CAD-). Compared to the control group CAD+ patients were characterized by increased 8-iso-PGF2α levels (P = 0.007) and reduced activity of PON-1 towards paraoxon (PONase, P = 0.002) and phenyl acetate (AREase, P = 0.037). Univariate correlation analysis indicated that 8-iso-PGF2α concentrations were positively associated with the severity of CAD as evaluated by the Gensini score (R = 0.41, P < 0.001) while PONase activity (R = -0.26, P < 0.05) and AREase activity (R = -0.23, P < 0.05) were inversely correlated with CAD severity. PONase activity and 8-iso-PGF2α concentration remained independent determinant of atherosclerosis severity in multiple linear regression after adjusting for age, gender, smoking habits, hypertension, type 2 diabetes, statin therapy, and HDL-C and TAG concentration (β coefficients -0.267; P < 0.05 and 0.368; P < 0.001, resp.). The results suggest that PON-1 activity and 8-iso-PGF2α concentration are associated with the presence and extent of coronary stenosis and may be considered additional markers of coronary artery disease.

Background/aims: Recent experimental studies have suggested that various cytokines may be important players in the development and progression of pancreatic cancer. However, these findings have not yet been verified in a clinical setting., Methods: In this study, we examined the levels of a broad panel of cytokines, including interleukin (IL)-1, IL-6, IL-8, IL-10, IL-12, IL-17, and IL-23, as well as tumor necrosis factor alpha (TNFα) and granulocyte-colony stimulating factor (G-CSF) in patients with pancreatic adenocarcinoma (n=43), other pancreatic malignancies (neuroendocrine [n=10] and solid pseudopapillary tumors [n=3]), and healthy individuals (n=41)., Results: We found that there were higher levels of IL-6, IL-8, IL-10 and TNFα in patients with pancreatic cancer compared to healthy controls (for all, at least p<0.03). Cancer patients had lower IL-23 concentrations than healthy individuals and patients diagnosed with other types of malignancies (for both, p=0.002). Levels of IL-6, IL-8, IL-10, and IL-23 were significantly associated with the direct number of circulating bone marrow (BM)-derived mesenchymal or very small embryonic/epiblast-like stem cells (SCs) in patients with pancreatic cancer. Moreover, our study identified a potential ability of IL-6, IL-8, IL-10, IL-23, and TNFα levels to enable discrimination of pancreatic cancer from other pancreatic tumors and diseases, including acute and chronic pancreatitis and post-pancreatitis cysts (with sensitivity and specificity ranging between 70%-82%)., Conclusions: Our study i) supports the significance of selected cytokines in the clinical presentation of pancreatic cancer, ii) highlights numerous associations between selected interleukins and intensified BMSCs trafficking in patients with pancreatic cancer, and iii) preliminarily characterizes the diagnostic potential of several cytokines as potential novel clinical markers of pancreatic cancer in humans.

Various experimental studies indicate potential involvement of bone marrow (BM)-derived stem cells (SCs) in malignancy development and progression. In this study, we comprehensively analysed systemic trafficking of various populations of BM-derived SCs (BMSCs), i.e., mesenchymal, haematopoietic, endothelial stem/progenitor cells (MSCs, HSCs, EPCs respectively), and of recently discovered population of very small embryonic/epiblast-like SCs (VSELs) in pancreatic cancer patients. Circulating CD133(+)/Lin(-)/CD45(-)/CD34(+) cells enriched for HSCs, CD105(+)/STRO-1(+)/CD45(-) cells enriched for MSCs, CD34(+)/KDR(+)/CD31(+)/CD45(-) cells enriched for EPCs and small CXCR4(+) CD34(+) CD133(+) subsets of Lin(-) CD45(-) cells that correspond to VSELs were enumerated and sorted from blood samples derived from 29 patients with pancreatic cancer, and 19 healthy controls. In addition, plasma levels of stromal-derived factor-1 (SDF-1), growth/inhibitory factors and sphingosine-1-phosphate (S1P; chemoattractants for SCs), as well as, of complement cascade (CC) molecules (C3a, C5a and C5b-9/membrane attack complex--MAC) were measured. Higher numbers of circulating VSELs and MSCs were detected in pancreatic cancer patients (P < 0.05 and 0.01 respectively). This trafficking of BMSCs was associated with significantly elevated C5a (P < 0.05) and C5b-9/MAC (P < 0.005) levels together with S1P concentrations detected in plasma of cancer patients, and seemed to be executed in a SDF-1 independent manner. In conclusion, we demonstrated that in patients with pancreatic cancer, intensified peripheral trafficking of selected populations of BMSCs occurs. This phenomenon seems to correlate with systemic activation of the CC, hepatocyte growth factor and S1P levels. In contrast to previous studies, we demonstrate herein that systemic SDF-1 levels do not seem to be linked with increased mobilization of stem cells in patients with pancreatic cancer., (© 2013 The Authors Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.)