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Being overweight or obese is a significant public health problem in the 21st century due to its scale, common existence and its cause-effect association with multiple diseases. Excessive accumulation of adipose tissue in humans is regarded as a major risk factor for development of cardiovascular and skeletal diseases. However, data from recent years have revealed that obesity is also strongly associated with increased risk of the majority of cancers in humans, including those originating from the gastrointestinal tract. During the last few year this association has been thoroughly proven and supported by several epidemiological analyses. The authors present i) the current state of knowledge regarding key (patho)mechanisms that link metabolism of human adipose tissue to development/progression of neoplasms (especially in the gastrointestinal tract), as well as ii) the results of selected clinical studies in which the influence of obesity on risk of gastrointestinal cancer development has been addressed. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The association between interleukin-1 polymorphisms, H. pylori and increased gastric cancer risk remains controversial. AIMS: To compare the prevalence of these polymorphisms in individuals with two mutually exclusive diseases connected with infection, gastric cancer, and duodenal ulcer. METHODS: 121 gastric cancer and 119 duodenal ulcer patients. Genomic DNA was typed for polymorphisms at position −511, −31 in the interleukin-1β gene (IL-1 β) using primer extension and mass-spectrometry. Analysis of the variable number of tandem repeats in intron 2, in its receptor antagonist gene (IL-1RN) was performed by PCR and agarose gel electrophoresis. RESULTS: All subjects were successfully genotyped for the three gene loci. IL-1 β-511 was found to be in reverse linkage disequilibrium with IL-1 β-31. The differences between gastric cancer and duodenal ulcer patients concerned only heterozygous variant of IL-1β and were related to family history of gastric cancer, tumor stage, histology, site. Thus, CT carriers were found to have a higher risk of sporadic [OR 2.21 (95% CI, 1.22–3.99)], early [OR 2.81 (95% CI, 1.14–6.93)], diffuse [OR 2.48, (95% CI 1.21–5.09)] or non-cardia gastric cancer [OR 1.88 (95% CI 1.06–3.33)]. Furthermore, CT genotype was significantly more prevalent in gastric cancer patients with negative than in those with a positive family history (p = 0.039). CONCLUSIONS: The association between the interleukin-1 polymorphisms and gastric cancer risk depends on the family history of gastric carcinoma in the study population. This phenomenon may be in part responsible for differences in results of interleukin-1 studies performed on populations with low and high gastric cancer prevalence. [ABSTRACT FROM AUTHOR]

Most pancreatic neuroendocrine tumors (PNETs) are indolent, while pancreatic ductal adenocarcinomas (PDACs) are particularly aggressive. To elucidate the basis for this difference and to establish the biomarkers, by using the deep sequencing, we analyzed somatic variants across coding regions of 409 cancer genes and measured mRNA/miRNA expression in nine PNETs, eight PDACs, and four intestinal neuroendocrine tumors (INETs). There were 153 unique somatic variants considered pathogenic or likely pathogenic, found in 50, 57, and 24 genes in PDACs, PNETs, and INETs, respectively. Ten and 11 genes contained a pathogenic mutation in at least one sample of all tumor types and in PDACs and PNETs, respectively, while 28, 34, and 11 genes were found to be mutated exclusively in PDACs, PNETs, and INETs, respectively. The mRNA and miRNA transcriptomes of PDACs and NETs were distinct: from 54 to 1659 differentially expressed mRNAs and from 117 to 250 differentially expressed miRNAs exhibited high discrimination ability and resulted in models with an area under the receiver operating characteristics curve (AUC-ROC) >0.9 for both miRNA and mRNA. Given the miRNAs high stability, we proposed exploring that class of RNA as new pancreatic tumor biomarkers. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is a significant problem worldwide. Most cancers are diagnosed at an advanced stage. Limited knowledge of the pathogenesis of pancreatic tumors results in limited diagnostic and therapeutic possibilities. Using metabolome analysis, we identified unique metabolite profiles specific not only for pancreatic ductal adenocarcinoma (PDAC) but also for neuroendocrine pancreatic tumor (PNET), which may be helpful to understand the pathogenesis of pancreatic diseases. Additionally, we discovered that disturbed metabolites, mainly acetylcarnitine C2, serotonin, and glycerophospholipid PC aa C34:1, have potential to be used as biomarkers for diagnosing and monitoring the progression of pancreatic tumors. Serum-circulating metabolites can be easily monitored without invasive procedures; they show the current condition of clinical patients and therefore help with pharmacological treatments or dietary strategies. 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. [ABSTRACT FROM AUTHOR]

Various experimental studies suggest that pancreatic malignancies may originate from stem cells. Recently we reported that in patients with pancreatic tumors intensified trafficking of selected populations of bone marrow (BM)-derived stem cells (SCs) is observed, and this is associated with activity of the complement cascade (Starzynska et al. JCMM 2013). Unfortunately the mechanisms responsible for this “selective” mobilization of BMSCs are not fully known. However, it is hypothesized that various chemokines may participate in this process. In this study we analyzed levels of interleukins (IL-1, IL-6, IL-8, IL-10, IL-12, IL-17 and IL-23) together with granulocyte-colony stimulating factor (G-CSF) and tumor necrosis factor-alpha (TNFα) in patients with pancreatic neoplasms (n =26) and control individuals (n =32), and verified whether these molecules are associated with previously observed phenomenon of selective BMSCs egress in patients with pancreatic neoplasms. Our results demonstrated that in patients with pancreatic neoplasms significantly (up to 3 times) higher levels of IL-6, IL-8, IL-10 and TNFα are observed (in all cases at least P <0.02), and lower IL-23 concentrations (P =0.002). No significant differences in IL-1, IL-12 nor G-CSF levels were stated. In our study, IL-6, IL-8 and TNFα levels negatively correlated with the absolute numbers of circulating hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPCs) (in all cases at least P <0.03), whereas IL-10 concentrations were associated with numbers of circulating very small embryonic/epiblast-like stem cells (VSELs) (r =0.57; P <0.05). Moreover, analysis of receiver operating characteristics (ROC) curves demonstrated relatively high values of area under ROC curve (between 0.70 and 0.83, in all cases at least P <0.01) for IL-6, IL-8, IL-10 and TNFα. Our study demonstrates that selected interleukins together with TNFα may be involved into orchestration of intensified BMSCs trafficking in patients with pancreatic tumors. Clinical value of these molecules must be assessed in further studies. Supported by MNiSW Grant (402 423038). [Copyright &y& Elsevier]

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). 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. 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. 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. [ABSTRACT FROM AUTHOR]

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), Helicobacterpylori 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 SDF1α in the PB of patients with CP. We noted a significant positive correlation between SDF1α 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. [ABSTRACT FROM AUTHOR]

(1) Background: stromal-derived factor-1 (SDF-1/CXCL12), hepatocyte and vascular-endothelial growth factors (HGF and VEGF) have been shown to facilitate cell motility, proliferation and promote local tumor progression and metastatic spread. Recent research shows the important role of these cytokines in gastric cancer (GC) progression. (2) Methods: 21 gastric cancer patients and 19 healthy controls were included in the study. SDF-1, HGF and VEGF levels were evaluated in sera by ELISA. Patients and control sera were used to stimulate CRL-1739 GC cell line, and chemotaxis, adhesion and proliferation potential were assessed. (3) Results: Concentrations of SDF-1, HGF and VEGF were significantly higher in patients than in controls. Chemotaxis and adhesion assays revealed a significant response of GC cells to patients' serum. Furthermore, significant relationships were seen between chemotactic/adhesion response and tumor stage. Serum from intestinal early GC patients produced significantly stronger chemotactic response when compared to patients with metastatic spread. In turn, serum from patients with distal metastases significantly increased the adhesion of GC cells when compared to sera from the patients with no distal metastases. We also observed that HGF strongly stimulated the proliferation of CRL-1739 cells. (4) Conclusions: We observed that the sera from GC patients, but also SDF-1, HGF and VEGF used alone, have a strong pro-metastatic effect on CRL-1739 cells. We also demonstrated that the concentration of these cytokines is specifically elevated in the sera of patients in an early stage of malignancy. Our results indicate that SDF-1, HGF and VEGF are very important molecules involved in gastric cancer progression. [ABSTRACT FROM AUTHOR]

A proton pump inhibitor (PPI) plus two antibiotics (amoxicillin and either clarithromycin or metronidazole) are recommended for treatment of acid-related disorders with Helicobacter pylori ( H. pylori) infection. The aim of this pharmacogenetic study was to evaluate the efficacy of triple therapy with PPIs on eradication of H. pylori infection in relation to cytochrome P450 2C19 ( CYP2C19) and P-glycoprotein ( MDR1) gene polymorphisms. The retrospective study involved 70 Polish Caucasian patients with H. pylori infection, diagnosed and treated with one of the two different triple therapy regimens [omeprazole, amoxicillin, and clarithromycin (OAC) or pantoprazole, amoxicillin, and metronidazole (PAM)]. Using genomic DNA, CYP2C19 ( *2 and *3) and C3435T MDR1 alleles were determined by means of polymerase chain reaction-restriction fragment length polymorphism assays. A significantly higher prevalence ( P<0.05) of heterozygous extensive metabolizers (hetEM) with CYP2C19*1/*2 genotype (32.4% versus 8.3%) and homozygous with 3435TT MDR1 genotype (38.2% versus 13.9%) was found in patients cured after the first cycle of triple therapy than in patients with failure of eradication after the first cycle. CYP2C19*1/*2 and 3435TT MDR1 genotypes as well as PAM regimen of treatment were also predictive of successful eradication of H. pylori infection after the first cycle of triple therapy at univariate/multivariate logistic regression analysis. This pharmacogenetic study on the influence of different CYP2C19 and C3435T MDR1 genotypes on H. pylori eradication suggests that CYP2C19 and MDR1 polymorphisms may be independent predictable determinants of the efficacy of triple therapy including PPI. The PAM regimen of treatment seems to be more effective after the first cycle of the therapy than the OAC regimen. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Gastric cancer (GC) in young patients is a troubling clinical problem. The aim of this study was to analyze whether patients ≤40 years of age with GC differ from patients (age >40 years) in terms of clinicopathological and selected genetic factors. Materials and methods: Between 1984 and 2011, data were collected for 840 GC patients diagnosed and treated for GC at the Department of Gastroenterology at Pomeranian Medical University. The following clinicopathological features were compared between two age groups: sex, symptom duration, family history of cancer, tumor site, stage (early vs. advanced), blood group, histology, Helicobacter pylori infection and BRCA2 C572T silent mutation status. Results: A total of 65 (7.7%) patients were age 40 years or younger. GC was predominant in women in the younger group (p <.001). Patients (≤40 years) more frequently reported a positive family history of cancer (p =.01) and a diffuse tumor type was more common in this group (p <.001). The two age groups did not differ significantly regarding symptom duration, tumor location or stage, H. pylori infection, blood group, or BRCA2 C572T silent mutation status. A comparison of male and female patients aged 40 years or less did not reveal sex-based differences in any analyzed features. Conclusion: Patients ≤40 years of age with GC differ from patient >40 years of age in having a predominance of women, diffuse tumor type, and positive family history of cancer. These results offer openings for further investigation of the relevance of these differences. [ABSTRACT FROM AUTHOR]

This article describes a patient with a severe relapse of newly diagnosed ulcerative colitis, with toxic megacolon, sclerosing cholangitis, and a Bauhin valve neuroendocrine neoplasm. The relationship between inflammatory diseases of the colon, cancer risk including neuroendocrine tumors, the potential impact of these tumors on the course of the underlying disease, and clinical differences between ulcerative colitis with and without coexisting sclerosing cholangitis are discussed based on the latest literature. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a leading cause of death in the western world, and its incidence increases with patient age. It is also known that with age there occur changes in the levels of certain hormones, including an increase in the secretion of pituitary gonadotropins (PtGs) as a result of the loss of gonadal hormone feedback. We recently reported that functional PtG receptors are expressed in human lung cancer cells, rhabdomyosarcoma cells, and malignant hematopoietic stem cells. Findings: Here we report for the first time that the receptors for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are expressed in primary tumor samples isolated from CRC patients as well as in the established human CRC cell lines HTC116 and HTB37. Moreover, we also report that PtGs stimulate chemotaxis, adhesion, and proliferation of these cell lines. Conclusions: Our results suggest that PtGs play an important and underappreciated role in CRC pathogenesis, and we call for further studies to better define their role in gastrointestinal malignancies and their direct effect on putative CRC cancer stem cells. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The case of a 76-year-old patient, with a history of melanoma, admitted to the department of gastroenterology with symptoms of hypovolemic shock, caused by massive gastrointestinal bleeding. Clot-covered melanoma metastases were detected in both gastroduodenoscopy and colonoscopy. Gastrointestinal melanoma metastases are found in the majority of patients with advanced melanoma during autopsy; however, they are rarely detected in intravital studies and can be misdiagnosed as other benign lesions in endoscopy. In cases of patients with history of melanoma, metastases should be considered as the cause of non-specific abdominal symptoms, anemia, or bleeding from the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Background. While cancer/testis antigens (CTAs) are restricted in postnatal tissues to testes and germ line-derived cells, their role in cancer development and the clinical significance of their expression still remain to be better defined. Objective. The aim of this study was to investigate the level of CTA expression in colon samples from patients with colorectal cancer (CRC) in relation to patient clinical status. Methods. Forty-five patients with newly diagnosed colorectal cancer were included in the study. We selected a panel of 18 CTAs that were previously detected in CRC as well as some new gene candidates, and their expression was detected at the mRNA level by employing RQ-PCR. Additionally, we evaluated CTA expression in three colon cancer cell lines (CL-188, HTB-39, and HTB-37) after exposure to the DNA methylation-modifying drug 5-azacytidine. Results. We report that 6 out of 18 (33%) CTAs tested (MAGEA3, OIP5, TTK, PLU1, DKKL1, and FBXO39) were significantly (p<0.05) overexpressed in tumor tissue compared with healthy colon samples isolated from the same patients. Conclusions. Moreover, we found that MAGEA3, PLU-1, and DKKL expression positively correlated with disease progression, evaluated according to the Dukes staging system. Finally, 5-azacytidine exposure significantly upregulated expression of CTAs on CRC cells, which indicates that this demethylation agent could be employed therapeutically to enhance the immune response against tumor cells. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is part of the spectrum of diseases linked to BRCA1 and BRCA2 mutations that increase the risk of breast and ovarian cancer. Data suggesting an increased risk of developing GC among BRCA1 and BRCA2 mutation carriers are based almost exclusively on indirect studies. The objective was to assess in a direct study whether there is a relationship between GC and selected recurrent BRCA1 and BRCA2 mutations in the Polish population. Methods: Three hundred seventeen GC patients (193 males and 124 females; mean age 59.5 ± 12.8 y) diagnosed at the Department of Gastroenterology at the Pomeranian Medical University were included in this retrospective study. All patients were genotyped for 3 BRCA1 Polish founder mutations (5382insC, C61G and 4153delA) as well as for 9 known recurrent mutations in BRCA1 and BRCA2 genes. Genotyping was performed using allele-specific oligonucleotide polymerase chain reaction (ASA-PCR) for 4153delA and 5382insC, restriction fragment length polymorphism (PCR-RFLP) for C61G and TaqMan real-time PCR for 185delAG, 3819del5, 3875del4, 5370C > T, 886delGT, 4075delGT, 5467insT, 6174delT and 8138del5. Results: Among tested mutations one founder BRCA1 mutation 5382insC was detected in two of 317 (0.63 %) GC cases. A comparison of frequency of detected BRCA1 founder mutations in GC patients to previously described 4570 Polish controls (0.63 % vs. 0.48 %) failed to indicate an increased risk of GC in the mutation carriers (OR = 1.3; 95 % CI 0.3-5.6, p = 0.71). A comparison of frequency of GC male cases and male controls (1.0 % vs. 0.43 %,OR = 1.5; 95 % CI 0.3-6.4, p = 0.61) allowed to formulate the same conclusion that there is no increased risk for GC for males. None of the 9 recurrent BRCA1 and BRCA2 mutations has been detected in tested GC patients. Conclusion: The current study indicates that founder BRCA1 mutations reported in Polish breast/ovarian cancer patients do not contribute to increased GC risk. The nine tested recurrent BRCA1 and BRCA2 mutations were not detected in GC patients which may suggests that they are rare in GC patients in the Polish population. Further analyses, including sequencing of entire sequences of BRCA1 and BRCA2 genes, are necessary to ultimately determine the role of these two genes in GC in Poland. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Complement-derived molecules modulate the intensity of renal ischemia–reperfusion injury and may lead to the generation of biochemical signals [such as stromal-derived factor-1 (SDF-1) or sphingosine-1-phosphate (S1P)], which stimulate tissue/organ regeneration after injury. We tested the association between perioperative C5b-9/membrane attack complex (MAC) levels and intensified erythrocyte lysis, and asked whether significant changes in the levels of pro-regenerative substances occur during the early phase of renal allograft reperfusion. Seventy-five recipients were enrolled and divided into the early, slow, and delayed graft function (DGF) groups. Perioperative blood samples were collected from the renal vein during consecutive minutes of reperfusion. Extracellular hemoglobin (eHb), albumin (plasma S1P transporter), 8-iPF2α-III isoprostane, SDF-1 and S1P concentrations were measured. Throughout the reperfusion period, erythrocyte lysis intensified and was most pronounced in the DGF group. However, perioperative eHb levels did not correlate significantly with C5b-9/MAC values, but rather with the intensity of oxidative stress. No significant changes were observed in S1P, its plasma transporter (albumin) or SDF-1 levels, which were relatively low in all groups throughout the reperfusion period. Our study therefore demonstrates that no known biochemical signal for bone marrow-derived stem cell mobilization is released from human renal allografts to the periphery during the early phase of reperfusion. [ABSTRACT FROM PUBLISHER]

The article presents updates on the treatment of gastric cancer patients which are provided by the Polish Study Group on Gastric Cancer (PGCSG). The changes included in a document consist of new classifications of stomach cancer advancement contributed by Japanese scientific research societies. A discussion on surgical treatment, combined treatment and the role of endoscopic treatment and less invasive method of treatment of early stomach cancer is provided.

Background: It has been suggested that action of complement cascade [CC]-derived anaphylatoxins/molecules may represent a missing link between obesity and metabolic disorders. However, to date, the direct biochemical/ immunomodulatory composition of the human AT environment remains poorly understood. In this study, we examined plasma and AT (subcutaneous and visceral/omental) levels of selected CC-derived anaphylatoxins/molecules, and adipsin as well as verified their associations with immune and stem cells chemoattractant - stromal-derived factor-1 (SDF-1). Methods: A total of 70 (35 subcutaneous and 35 omental) AT samples were obtained from patients undergoing elective surgery. Plasma and AT-derived interstitial fluid levels of C3a, C5a, C5b-9/membrane attack complex (MAC), complement factor D (adipsin) were measured using ELISA. Results: AT levels of all examined substances were significantly lower than the corresponding levels in the plasma (in all cases P < 0.0000001). Moreover, in subcutaneous AT, robust C3a and adipsin concentrations were observed, whereas high levels of C5b-9/MAC were detected in the visceral depots. In addition, we established the correlations between analyzed molecular substances and body composition, BMI and/or the adiposity index of the examined patients. Conclusions: Our study demonstrated for the first time that significantly reduced levels of complement-derived molecules were present in human AT than in the peripheral blood, and that these factors are associated with the metabolic status of examined individuals. Moreover, in human AT, various associations between complement-derived molecules and SDF-1 levels exist. [ABSTRACT FROM AUTHOR]

Nodular regenerative liver hyperplasia (NRH) is a very rare but potentially severe complication of thiopurine-containing immunosuppressive therapy for autoimmune disorders, organ transplantation, and/or oncological treatment. Here we report a case of a 40-year-old female patient with Crohn''s disease and genetic hypercoagulability disorder--factor V Leiden, who in the course of azathioprine immunosuppressive treatment for inflammatory bowel disease developed NRH, which was clinically manifested by thrombocytopenia and delicate hepato-splenomegaly. Moreover, her endoscopic examination of upper gastrointestinal tract demonstrated esophageal varices. Genetic analysis revealed heterozygous genotype (**1/**3A) of thiopurine S-methyltransferase (TPMT), a key enzyme of thiopurines'' metabolism, which results in lower activity of TPMT enzyme, thereby making our patient more susceptible to azathioprine-related hepato and myelotoxicity development. Treatment was started with the immediate cessation of azathioprine therapy, and administration of propranolol as primary prophylaxis for bleeding from esophageal varices. Currently (3 years after diagnosis) remission of Crohn''s disease is achieved, however, progression of features of portal hypertension is observed. Propranolol administration is continued and the patient is constantly monitored in our Department. Our Case Study highlights the clinical difficulties and challenges associated with diagnosing of azathioprine-induced NRH, as well as, supports previous observations that hypercoagulability disorders and abnormal TPMT activity may contribute to NRH development. [ABSTRACT FROM AUTHOR]

Eradication of Helicobacter pylori is an important treatment strategy in peptic ulcer patients. Current regimens of eradication consist of proton pump inhibitor (PPI) and two antibiotics. The principal enzyme involved in PPIs metabolism is CYP2C19, which exhibits an interindividual variability of activity, mainly due to genetic polymorphism. Two alleles ( CYP2C19*2 and CYP2C19*3), responsible for slow PPIs metabolism, were previously associated with higher efficacy of eradication. Recently, a novel CYP2C19 gene variant ( CYP2C19*17), associated with faster metabolism of CYP2C19 substrates, was described. In the present study, a potential association between CYP2C19*17 allele and lower H. pylori eradication efficacy was tested in a group of peptic ulcer patients. A total of 125 peptic ulcer patients, positive for H. pylori infection, were treated with triple therapy (pantoprazole+amoxicillin+metronidazole). Subsequently, the patients were divided into two groups (group 1 – success, and group 2 – failure of eradication after therapy) and genotyped for the presence of CYP2C19 variant alleles (*2, *3, and *17). Frequency of CYP2C19 alleles in two groups of patients were: 56.4 versus 65 ( p=0.060) for *1, 15.4 versus 5.3 ( p=0.015) for *2, and 28.2 versus 25.5 ( p=0.663) for *17 allele, respectively. CYP2C19*3 was not detected in the evaluated population. No significant differences in frequency nor distribution of *17 allele were found between two groups of patients. CYP2C19*2 allele was associated with successful H. pylori eradication ( p<0.02), *2 allele carriers were found to be over 4-times more prone to the treatment compared to *1/*1 homozygotes (OR=4.2, p=0.015). Our results suggest that, contrary to CYP2C19*2, CYP2C19*17 allele has no impact on efficacy of H. pylori eradication in peptic ulcer patients treated with pantoprazole. [ABSTRACT FROM AUTHOR]

Germ-line mutations in the BRCA2 gene are associated with a wide range of cancer types, including the breast, ovary, pancreas, prostate and melanoma. In this study, we evaluated the importance of a family history of stomach cancer in predicting the presence of a BRCA2 mutation in Polish patients with ovarian cancer. A BRCA2 mutation was found in eight of 34 women with ovarian cancer and a family history of stomach cancer versus three of 75 women with ovarian cancer and a family history of ovarian cancer, but not of stomach cancer (odds ratio=7.4; 95% CI 1.8-30; P=0.004). The results of this study suggest that, in the Polish population, the constellation of ovarian and stomach cancer predicts the presence of a germ-line BRCA2 mutation and confirms that stomach cancer is part of the spectrum of BRCA2 mutations. It is expected that the penetrance of BRCA2 mutations for stomach cancer will vary from country to country, reflecting local environmental and lifestyle factors.European Journal of Human Genetics (2003) 11, 955-958. doi:10.1038/sj.ejhg.5201064 [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates the potential effect of microbiota on the pathogenesis and course of schizophrenia. However, the effects of olanzapine, second-generation antipsychotics, on gut microbiota have not been investigated in humans. This study aimed to analyze fecal microbiota in schizophrenia patients treated with olanzapine during six weeks of their hospital stay. After a seven-day washout from all psychotropic medications, microbiota compositions were evaluated at baseline and after six weeks of hospitalization using 16S rRNA sequencing. The study was conducted in 20 inpatients, who followed the same hospital routine and received 5–20 mg daily doses of olanzapine. Olanzapine treatment was associated with clinical improvements in all patients and significant increases in body mass index in females, but not changes in gut microbiota compositions and predicted function. The severity of symptoms at the beginning of treatment varied in accordance with the predicted metabolic activity of the bacteria. The present findings indicate that the microbiota of schizophrenia patients is highly individual and has different taxonomical (Type 1, with a predominance of Prevotella, and Type 2 with a higher abundance of Bacteroides, Blautia and Clostridium) and functional clusters, and it does not change following six weeks of olanzapine therapy; in addition, the microbiota is not associated with either the weight gain observed in women or the effectiveness of olanzapine therapy. [ABSTRACT FROM AUTHOR]

Recently there has been heightened interest in the potential significance of interleukin (IL)-17 and IL-23 in the development/progression of human malignancies. Here, we analyzed the systemic levels of these cytokines in 75 patients with different types of gastric neoplasms (carcinoma, gastrointestinal stromal tumors, neuroendocrine neoplasms, and lymphomas) and 42 healthy volunteers. We found that patients with all types of gastric neoplasms have significantly lower IL-23 levels. However, in comparison to the levels in healthy individuals, IL-17 concentrations were lower only in patients with types of gastric neoplasms other than carcinoma. Interestingly, IL-17 levels significantly differed between patients with early and advanced gastric carcinoma. No significant associations were detected between the systemic levels of examined interleukins and TNM staging. However, peripheral levels of IL-23 were correlated with the absolute numbers of circulating populations of bone marrow-derived mesenchymal and very small embryonic/epiblast-like stem cells in patients with gastric carcinoma. ROC curve analyses demonstrated that systemic levels of IL-17 seem to meet basic criteria for consideration as a helpful diagnostic marker in the detection of gastric carcinoma. In conclusion, our study provides translational evidence confirming the clinical significance of IL-17 and IL-23 in the pathogenesis of different types of gastric neoplasms in humans. [ABSTRACT FROM AUTHOR]

Recently, there has been a growing interest in the importance of stem cells (SCs) in the development/progression of gastric neoplasms. In this study, we performed a comprehensive analysis of different populations of bone-marrow-derived stem cells (BMSCs) in patients with various types of gastric malignancies, including gastric cancer, gastrointestinal stromal tumors (GISTs), neuroendocrine neoplasms (NENs), and lymphomas. We found significantly lower numbers of circulating Lin-/CD45 +/ CD133 + hematopoietic stem/progenitor cells (HSPCs), and intensified peripheral trafficking of both Lin−/CD45−/CXCR4+/CD34+/CD133+ very small embryonic/epiblast-like stem cells (VSELs) and CD105 + /STRO-1 +/ CD45- mesenchymal SCs (MSCs) in patients with gastric cancer, but not in those with other types of gastric neoplasms. No significant differences in the absolute numbers of circulating CD34 +/ KDR +/ CD31 +/ CD45- endothelial progenitor cells (EPCs) were observed between the groups. This abnormal balance in the peripheral trafficking of BMSCs in patients with gastric cancer was neither associated with clinical stage of the disease nor with systemic levels of stromal-derived factor-1 (SDF-1), as these were comparable to the values observed in control individuals. Interestingly, the absolute numbers of circulating BMSCs correlated with the concentrations of complement cascade-derived anaphylatoxins/molecules (mainly C5b-9/membrane attack complex-MAC) and sphingosine-1-phosphate (S1P). In summary, our translational study revealed that abnormal peripheral trafficking of BMSCs occurs in patients with gastric cancer, but not in those with other types of gastric neoplasms. Further, our findings indicate that highlighted complement cascade-derived molecules and S1P, but not SDF-1, are significant players associated with this phenomenon. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that action of complement cascade [CC]-derived anaphylatoxins/molecules may represent a missing link between obesity and metabolic disorders. However, to date, the direct biochemical/immunomodulatory composition of the human AT environment remains poorly understood. In this study, we examined plasma and AT (subcutaneous and visceral/omental) levels of selected CC-derived anaphylatoxins/molecules, and adipsin as well as verified their associations with immune and stem cells chemoattractant - stromal-derived factor-1 (SDF-1).Methods: A total of 70 (35 subcutaneous and 35 omental) AT samples were obtained from patients undergoing elective surgery. Plasma and AT-derived interstitial fluid levels of C3a, C5a, C5b-9/membrane attack complex (MAC), complement factor D (adipsin) were measured using ELISA.Results: AT levels of all examined substances were significantly lower than the corresponding levels in the plasma (in all cases P < 0.0000001). Moreover, in subcutaneous AT, robust C3a and adipsin concentrations were observed, whereas high levels of C5b-9/MAC were detected in the visceral depots. In addition, we established the correlations between analyzed molecular substances and body composition, BMI and/or the adiposity index of the examined patients.Conclusions: Our study demonstrated for the first time that significantly reduced levels of complement-derived molecules were present in human AT than in the peripheral blood, and that these factors are associated with the metabolic status of examined individuals. Moreover, in human AT, various associations between complement-derived molecules and SDF-1 levels exist. [ABSTRACT FROM AUTHOR]