Nasal allergen and methacholine provocation tests influence co­expression patterns of TGF­ß/SMAD and MAPK signaling pathway genes in patients with asthma.

Asthma is characterized by chronic bronchial inflammation and is a highly heterogeneous disease strongly influenced by both specific and non-specific exogenous factors. The present study was performed to assess the effect of nasal allergen provocation tests and methacholine provocation tests on the mRNA co-expression patterns of genes (SMAD1/3/6/7, MPK1/3 and TGFB1/3) involved in SMAD and non-SMAD TGF-ß signaling pathways in patients with asthma. Reverse transcription-quantitative PCR was performed on blood samples taken pre-provocation and 1 h post-provocation to assess gene expression changes. Of the 59 patients studied, allergen provocations were administered to 27 patients and methacholine provocations to 32 patients. Correlations between expression levels of studied genes were found to be influenced markedly by the challenge administered, challenge test result and time elapsed since challenge. Importantly, increases in expression levels for four gene pairs (MAPK1-SMAD3, MAPK3-SMAD3, SMAD1-SMAD3 and SMAD3-TGFB1) were found to correlate significantly with asthma occurrence in the allergen provocation cohort, but not in the methacholine provocation cohort. The present study allows us to draw the conclusion that both intranasal allergen and bronchial methacholine challenges influence mRNA co-expression patterns of the SMAD1/3/6/7, MPK1/3 and TGFB1/3 genes.

Analysis of Spermine Oxidase gene and proinflammatory cytokines expression in gastric cancer patients with and without Helicobacter pylori infection - A pilot study in Polish population.

PURPOSE: Many types of cancer have infectious origins. Gastric cancer patients can demonstrate high seroprevalence of Helicobacter pylori (H. pylori). The aim of the present study was to assess the expression of SMOX gene in the group of Polish patients with gastric cancer. SMOX is believed to promote H. pylori-induced carcinogenesis via inflammation, DNA damage and activation of ß-catenin signaling. We also assessed the mRNA expression of selected pro-inflammatory cytokines, i.e. IL-2, IFN-γ, TNF-α, and antimicrobial peptide, cathelicidin. MATERIALS/METHODS: The study material consisted of gastric tissue samples collected during total gastrectomy from three different places in stomach: from primary tumor, 3 â€‹cm away from the primary lesion, and from the wall opposite to the primary tumor. After RNA isolation, qPCR reactions were performed for the relevant genes. RESULTS: The obtained results confirmed an increased level of SMOX expression in gastric cancer patients with the history of H. pylori infection. And, as far as we know, this is the first study on SMOX gene expression conducted on tissue taken from a patient, not on a cell line. The levels of pro-inflammatory cytokines, i.e. IL-2, IFN-γ, TNF-α, were also increased, thus indicating their contribution to the specific inflammatory microenvironment of the tumor. Interestingly, the levels of CAMP, encoding antimicrobial peptide, were reduced in all tissue types. CONCLUSIONS: The findings confirm that SMOX plays a role in gastric carcinogenesis. However, further research is needed on the role of inflammatory and other factors involved in this process to identify targets for cancer immunotherapy.

An unusual non­metastatic, mismatch repair­deficient primary gastric squamous cell carcinoma presenting as a large, exophytic, bleeding tumor: A case report.

Primary gastric squamous cell carcinoma (GSCC) is an extremely rare malignancy with a poor prognosis. Despite the improved knowledge regarding its pathogenesis and biology, the treatment options remain limited. The present study reported on the unique case of a mismatch repair-deficient (dMMR) primary GSCC in a 79-year-old woman reporting fatigue and symptoms of upper gastrointestinal tract bleeding. Physical examination revealed abdominal pain at palpation. Gastroscopy revealed a large, exophytic, bleeding tumor. Medical imaging confirmed a mushroom-like polyp in the lumen of the stomach, with no signs of disease spread. Total gastrectomy and D2 lymphadenectomy were performed. Pathological examination of the post-operational material confirmed a well-differentiated SCC invading the mucosa, submucosa and muscle layer. There were no signs of dissemination observed in any of the 32 excised lymph nodes. Notably, according to the last follow-up, the patient remains well, supporting the 5-year GSCC survival rate statistics. To the best of our knowledge, this is the first such GSCC case reported in the Surgical Oncology Outpatient Clinic (Copernicus Memorial Hospital, Lodz, Poland) and these findings add to the limited data on GSCC. Although this is a very rare condition, it should always be considered during the process of diagnosis of gastric tumors.

The Ratio of the Size of the Abdominal Aortic Aneurysm to That of the Unchanged Aorta as a Risk Factor for Its Rupture.

BACKGROUND: A ruptured abdominal aortic aneurysm is a severe condition associated with high mortality. Currently, the most important criterion used to estimate the risk of its rupture is the size of the aneurysm, but due to patients' anatomical variability, many aneurysms have a high risk of rupture with a small aneurysm size. We asked ourselves whether individual differences in anatomy could be taken into account when assessing the risk of rupture. METHODS: Based on the CT scan image, aneurysm and normal aorta diameters were collected from 186 individuals and compared in patients with ruptured and unruptured aneurysms. To take into account anatomical differences between patients, diameter ratios were calculated by dividing the aneurysm diameter by the diameter of the normal aorta at various heights, and then further comparisons were made. RESULTS: It was found that the calculated ratios differ between patients with ruptured and unruptured aneurysms. This observation is also present in patients with small aneurysms, with its maximal size below the level that indicates the need for surgical treatment. For small aneurysms, the ratios help us to estimate the risk of rupture better than the maximum sac size (AUC: 0.783 vs. 0.650). CONCLUSIONS: The calculated ratios appear to be a valuable feature to indicate which of the small aneurysms have a high risk of rupture. The obtained results suggest the need for further confirmation of their usefulness in subsequent groups of patients.

Analysis of miR-143, miR-1, miR-210 and let-7e Expression in Colorectal Cancer in Relation to Histopathological Features.

BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules involved in the control of the expression of many genes and are responsible for, among other things, cell death, differentiation and the control of their division. Changes in miRNA expression profiles have been observed in colorectal cancer. This discovery significantly enriches our knowledge of the pathogenesis of colorectal cancer and offers new goals in diagnostics and therapy. AIM: The aim of this study was to analyze the expression of four miRNA sequences-miR-143, miR-1, miR-210 and let-7e-and to investigate their significance in the risk of developing colorectal cancer. MATERIALS AND METHODS: miRNA sequences were investigated in formalin-fixed, paraffin-embedded (FFPE) tissue in colorectal cancer patients (n = 150) and in cancer-free controls (n = 150). The real-time PCR method was used. RESULTS: This study revealed a lower expression of miR-143 in colorectal cancer patients than in the controls. miR-143 was positively correlated with the degree of tumor differentiation (grading). Three out of four analyzed miRNA (miR-1, miR-210 and let-7e) were found to be statistically insignificant in terms of colorectal carcinoma risk. CONCLUSIONS: miR-143 may be associated with the development of colorectal cancer.

Gender-Specific Coagulation Profiles of Peripheral and Portal Blood May Help to Differentiate Malignant from Benign Pancreatic Tumour-Pilot Study.

Objective: Pancreatic adenocarcinoma (PDAC) and mass forming chronic pancreatitis (CP) can be easily misdiagnosed due to their resemblances in clinical, radiological, and biochemical criteria. In our previous study, we reported a very high concentration of D-Dimers in portal blood in patients with pancreatic cancer which may help to differentiate malignant from benign pancreatic tumours. In this study, we aim to describe other portal and peripheral coagulation profiles of PDAC in comparison to CP patients, as well to test the hypothesis; thus, it is possible to distinguish pancreatic malignancy and benign tumour based on these parameters. Methods: We included retrospectively 115 patients with the absence of venous thromboembolism (VTE), qualified to surgical treatment due to pancreatic tumours, both PDAC and CP. Patients underwent surgery in General and Transplant Surgery Unit of Medical University of Lodz between December 2011 and February 2014. Patients with distant metastases diagnosed before or during the surgery were excluded. The coagulation profile, which includes fibrinogen, activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT), was determined in blood samples from the portal and peripheral vein taken intraoperatively. Results: The fibrinogen level was higher and the aPTT index shortened in the peripheral and portal blood of the PDAC group, which reflects the well-known link between PDAC and general hypercoagulability. Furthermore, these effects are sex-specific. The mean age in the CP group was lower than in the PDAC group (54.63 ± 12.37 vs. 63.77 ± 3.23, p < 0.001) and correlated with the fibrinogen distribution in male patients with CP (portal r = 0.34; p = 0.07; peripheral r = 0.39; p = 0.04). We calculated sex-specific logistic regression models (male: peripheral aPTT and age, AUC: 0.795, female: portal fibrinogen and age, AUC: 0.805), both maintaining the good discrimination properties after V-fold cross validation (0.759, 0.742). Conclusions: Our study shows that the differences between coagulation profiles in PDAC and CP patients not only seems to be a reflection of gender-specific biological features, but also helps to discriminate between them. The main goal of the study was to explore the biology of pancreatic cancer and lay a solid base for further investigations of PDAC biomarkers. This paper is the first to describe the detailed coagulation profile in portal blood in patients with pancreatic solid tumors. At present, the clinical application of our results is not clear; however, we hope that it may improve our understanding of this complex disease.

FT3 to FT4 Conversion Ratio May Be an Independent Prognostic Factor in Pancreatic Cancer Patients.

Preclinical evidence suggests that T4 can promote tumor growth while T3 can act conversely; therefore, the fT3 and fT4 concentrations should affect overall survival (OS) in cancer patients. The objective of the study was to look for an association between thyroid hormone concentrations in peripheral blood and OS in the pancreatic adenocarcinoma (PDAC) patients group. We included, retrospectively, 15 PDAC patients, without thyroid dysfunction under treatment, who underwent radical surgery, with no prior history of anticancer therapy. TSH, fT3, and fT4 concentrations were determined in blood samples taken preoperatively. We found that the fT3/fT4 ratio categorized into two groups (<0.22 vs. ≥0.22) dichotomized the study population into poor and good prognosis subgroups (log-rank p = 0.03; OS medians, respectively: 3 and 14 months), being a statistically significant predictor both in uni- and multivariate Cox regression analysis. We conclude that the importance of fT4 into fT3 conversion means not just its standard metabolic effects as the final products of thyroid gland activity. We hypothesize that it is linked to the progression of pancreatic malignancies, either via thyroid hormone receptors or indirectly, by interaction with cancer cells product.

Tension-Free Hiatal Hernia Repair Using Ligamentum Teres in Paraoesophageal Hernia Treatment.

AbstractIntroductionType II and III (paraoesophageal and mixed) hiatal hernia treatment remains a technically difficult procedure carrying a risk of complications and recurrence as high as 40%. Using synthetic meshes entails possible serious complications; efficacy of biologic materials remains unclear and requires further research.AimThe aim of the article was to present the centres experience of type II and III large hiatal hernia treatment using the ligamentum teres and to draw attention to potential benefits of conducted procedures.Material and MethodsThe study enrolled 6 patients: 3 women and 3 men aged 37-58 with radiologically and endoscopically confirmed large paraoesophageal hernias. The patients underwent Nissen fundoplication and hiatal hernia repair using the ligamentum teres. The patients were followed up for six months with subsequent radiological and endoscopic assessment.ResultsDuring the six-month follow-up no clinical or radiological characteristics of hiatal hernia recurrence were observed in the patients. Two patients reported symptoms of dysphagia; mortality was 0%.ConclusionsHiatal hernia repair using the vascularized ligamentum teres may constitute an effective and safe method of large hiatal hernia repair.