Rectal neuroendocrine tumors in a colon cancer screening colonoscopy program. Sixteen-year single institution experience.

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.

Immunohistochemical expression of PARP-1 in triple-negative endometrial cancer - a comparison of different score systems.

Endometrial cancer is the most common malignant neoplasm of the female reproductive system. The number of diagnosed cases is increasing every year. In recent years, the triple-negative phenomenon (TNP) has been identified as one of the determinants of shorter survival in endometrial cancer patients. The aim of the study was to compare the PARP-1 protein expression in triple-negative (TNEC) and non-triple-negative (NTNEC) endometrial cancer patients and determine the relationship between the PARP-1 protein expression in endometrial cancer cells and patient's overall survival depending on the adopted scale (H-SCORE < 75, H-SCORE < 50, Allred scale). The study involved 265 patients with histopathologically confirmed endometrial cancer. The patients were divided into 2 groups: patients with TNEC and patients with NTNEC. The study was conducted using a tissue microarray technique. Expression of PARP-1 protein was determined by immunohistochemistry. Protein expression evaluation was performed using virtual microscopy and the Image Scope computer image analysis system. The following conclusions were reached: total and individual levels of nuclear or cytoplasmic PARP-1 expression varied with the presence or absence of TNP, and PARP-1 nuclear expression at the 2+ level had a significant effect on the increased risk of death (according to H-SCORE < 75).

Molecular classification of glioblastoma based on immunohistochemical expression of EGFR, PDGFRA, NF1, IDH1, p53 and PTEN proteins.

Glioblastoma (GBM) is the most common and most aggressive primary tumor of the central nervous system. Current GBM treatments have low effectiveness. This is mainly due to the high degree of heterogeneity of GBM tumors. Despite similarities in the classic microscopic image, these tumors differ significantly in molecular terms. The aim of the study was to classify GBM tumors into one of four molecular types based on the immunohistochemical expression of EGFR, PDGFRA, NF1, IDH1, p53 and PTEN proteins and find the association between individual glioma molecular types and prognostic clinical and morphological parameters. From the group of 162 patients the classical molecular type of tumor was observed in 17 (10%) patients, in 23 (14%) the tumor was mesenchymal, in 32 (20%) proneural, and in 90 (56%) neural. No significant relationship was observed between the molecular type of GBM tumors and the studied clinical and morphological parameters of prognostic significance. There were also no statistically significant correlations between the GBM tumor molecular type and survival, both in terms of overall survival and relapse-free survival. Analyzing the impact of all prognostic variables and molecular type of GBM on the probability of overall survival, statistically significant relationships were found.

Clinical efficacy of p16/Ki-67 dual-stained cervical cytology in secondary prevention of cervical cancer.

Cervical cancer is the third most common malignant neoplasm in women worldwide. HPV infection is the necessary factor for the cancer to develop. HPV DNA can be integrated into the genome of squamous epithelium and cause transcription of the viral oncoproteins and development of invasive cancer within 15-20 years. We assessed ICC co-expression of p16/Ki-67 proteins in smears collected from the uterine cervix and the association between p16/Ki-67 co-expression and cytologic and histologic results. Samples were collected from 93 women using liquid based cytology (LBC). Two microscopic slides were prepared: for Papanicolaou staining and ICC staining. Biopsy samples were collected from 43 women. Diagnosis of CIN 2+ was the endpoint of the study. p16/Ki-67 positive cells were found in women with: 1) a cytology result of ASC-US (3.59%), LSIL (2.22%), ASC-H (21.92%), HSIL (33.18%), SCC (72.22%) or NILM (3.44%); 2) a histopathologic result of CIN 1 (2.13%), CIN 2 (19.93%), CIN 3 (23.22%), SCC (69.72%) or normal histology (7.58%). p16/Ki-67 dual staining can increase the efficiency of screening methods and indicate women in whom further diagnostic procedures are required or those with extremely low risk of cancer. Sparing protocols will have a significant role in women of reproductive age.

Clinicopathologic characteristics and resection rates of papillary early gastric cancer removed by endoscopic submucosal dissection.

The aim of this study was to assess the: 1) clinicopathologic features of papillary early gastric cancer (PEGC) (13 cases) compared to tubular early gastric cancer (TEGC) (41 cases); 2) efficiency of endoscopic submucosal dissection (ESD) in treatment of PEGC. From January 2007 to February 2016, a total of 54 consecutive patients with early gastric cancer (EGC) underwent ESD at the Department of Gastroenterology of the Pomeranian Medical University in Poland. The histologic type of carcinoma was assessed according to the WHO histological classification of GC. The extension of GC into the submucosa was measured using the Aperio Scan Scope image analysis system tools. PEGCs were diagnosed in 24.1% of the cases of EGC. PEGCs were significantly more elevated in macroscopic examination and better demarcated tumors than TEGC. There were no significant differences between gender, tumor location, ulceration, tumor size, depth of invasion (T), presence of intestinal metaplasia and lymphocytic infiltrate. Curative resection was achieved in 87.1% of patients with EGCs treated with ESD. The lower rate of curative resection (R0) observed in PEGC (76.9%) vs TEGC (90.2%) was not statistically significant. Further studies will be necessary to confirm the clinical and morphological presentation of PEGCs.

Triple negative endometrial cancer.

Endometrial cancer (EC) is the most common malignancy of the female genital tract in the developed countries. In Poland, EC incidence increased from 3.496 to 5.251 between 2000 and 2011, with 5.251 new cases were diagnosed in 2011 alone, and this upward trend is expected to continue. There are two types of endometrial cancer: estrogen- related type I (approximately 80% of the cases) and unrelated to estrogen type II. Type I includes adenocarcinomas which grow slowly, have better prognosis, superficially infiltrate the myometrium, originate from endometrial hyperplasia without atypia, and occur before and after menopause. The most common type I mutations include PTEN, KRAS and microsatellite instability. Type II is represented by serous, mucinous, clear-cell carcinomas, with aggressive behavior associated with poor prognosis, high risk of distant metastases at diagnosis, deeper infiltration of the uterine muscle, often to serosa, originating from the atrophic endometrium, and typically presenting after menopause. The most common type II mutations include TP53, HER-2 and P16.

Histomorphologic features of early gastric carcinoma treated by endoscopic submucosal dissection: relation to efficiency of endoscopic resection.

OBJECTIVE: Early gastric cancer (EGC) is defined as cancer invasion confined to the mucosa or submucosa, irrespective of lymph node metastasis. Recently endoscopic submucosal dissection (ESD) has been widely accepted for the treatment for dysplasia and EGC without lymph node metastases. While the method has been advanced in Far East countries, ESD is still being developed in Europe and has not gained enough popularity although it has been recommended as the treatment of choice for superficial gastric neoplastic lesions by European Society of Gastrointestinal Endoscopy (ESGE) in 2015. METHODS: The aim of the study was to perform a retrospective analysis of clinical and histomorphologic features of 58 cases of EGCs removed by ESD in a university hospital in Western Pomerania in Poland and to evaluate factors related to the efficiency of ESD resection. RESULTS: With univariate analysis, indications for ESD with the highest R0 rate were found in EGCs limited to mucosa (T1a, small mucosal, M), without muscularis mucosa invasion, localised in the middle/lower part of stomach and intestinal type in histological examination. The R0 complete resection rate was significantly (p < 0.0001) lower for T1b than that for T1a tumours (21.4% vs. 100%). Tumours with submucosal involvement were associated with lower efficiency of ESD procedure. CONCLUSIONS: Our data showed that in EGCs with favourable histomorphologic characteristics, ESD seemed to be a totally efficient and safe method of treatment in a European small-volume centre. R0 resection rate reached 81.1% of cases and median time of the ESD procedure was 61.5 min.

Expression of Mismatch Repair Proteins in Early and Advanced Gastric Cancer in Poland.

BACKGROUND Mutations in DNA of mismatch repair (MMR) genes result in failure to repair errors that occur during DNA replication in microsatellites, resulting in accumulation of frameshift mutations in these genes and leading to DNA mismatch replication errors and microsatellite instability. Gastric cancers (GCs) with high MSI (MSI-H) are a well-defined subset of carcinomas showing distinctive clinicopathological features. In this study we investigated the rate of MSI and the correlation between MSI status and clinicopathological features of GC. MATERIAL AND METHODS The study included 107 patients with GCs: 61 with advanced gastric cancers (AGC) and 46 with early gastric cancer (EGC). MSI deficiency in GCs was assessed by the immunohistochemical analysis of expression of MMR proteins - MLH1, MSH2, MSH6, and PMS2 - using formalin-fixed and paraffin-embedded tissue. RESULTS A total of 6 (5.6%) MSI-H were observed. The loss of MMR proteins expression was associated with the intestinal type of GC in Lauren classification, and tubular and papillary architecture in WHO classification. There was no statistically significant association between negative MMR expression and other selected clinical parameters: age, sex, tumor location, depth of invasion (EGC and AGC), lymph nodes status, presence of the ulceration, and lymphocytic infiltrate. CONCLUSIONS In the present era of personalized medicine, the histological type of GC and MMR proteins status in cancer cells are very important for the proper surveillance of patients with familial GC and sporadic GCs, as well as for selecting the proper follow-up and treatment. Larger collaborative studies are needed to verify the features of MSI-H GCs in Poland.

The role of Nrf2 in pathology of pleomorphic adenoma in parotid gland.

BACKGROUND: Pleomorphic adenoma (benign mixed tumor) is one of the most common salivary gland tumors. However, the processes involved in its carcinogenesis are not well defined. This study aimed to define the contribution of Nfr2 (nuclear factor (erythroid-derived 2)-like 2) to pleomorphic adenoma pathology. The Nrf2-controlled gene system is one of the most critical cytoprotective mechanisms, providing antioxidant responses. MATERIAL AND METHODS: The study was carried out in pleomorphic adenoma and control parotid gland tissues, investigating gene expression of NFE2L2, as well as KEAP1 (Kelch-like ECH-associated protein 1) and NQO1 (quinone oxidoreductase), at mRNA and protein (immunohistochemistry) levels. Functional evaluation of Nrf2 system in the parotid gland was evaluated in HSY cells (human parotid gland adenocarcinoma cells). RESULTS: Pleomorphic adenoma specimens showed cytoplasmic and nuclear Nfr2 expression in epithelial cells, as well as more variable lower Nrf2 level in mesenchymal cells. In the parotid gland, Nrf2 was expressed in cytoplasm of serous, mucous, and duct cells. Nuclear Nrf2 expression was predominantly seen in serous cells, whereas mucous and duct cells were mostly negative. Comparable mRNA levels of NFE2L2 and NQO1 genes and significantly higher expression of KEAP1 in pleomorphic adenoma were seen. HSY cell incubation with oltipraz demonstrated significant elevation of NFE2L2 after 24 and 48 hours of stimulation, whereas NQO1 was elevated, but significantly only after 24 hours, and KEAP1 expression remained unchanged. CONCLUSIONS: Summarizing both in vitro and in vivo observations, it can be stated that Nrf2 may play a role in the pathology of pleomorphic adenoma.

PARP-1 expression in CD34+ leukemic cells in childhood acute lymphoblastic leukemia: relation to response to initial therapy and other prognostic factors.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein that impacts DNA repair and apoptosis. Both experimental and ongoing clinical studies indicate that PARP-1 inhibitors are potent and promising anticancer agents. However, the outcome of treatment with PARP-1 inhibitors depends on the expression of PARP-1 protein in the tumor cells. This study aimed to assess PARP-1 expression in peripheral blood CD34+ leukemic cells before and after 12 hours of prednisone administration as well as the relation between PARP-1 expression and early treatment response to initial therapy and other prognostic factors (immunophenotype, age, initial peripheral blood white blood count [WBC], and risk factor group). The study comprised 43 children with de novo ALL. Cytospins of peripheral blood were stained with mouse anti-CD34-FITC and anti-PARP-1 antibody followed by goat anti-mouse APC-conjugated antibody. DNA was counterstained with PI (propidium iodide). Cellular fluorescence was measured by a laser scanning cytometer. Statistically significant differences in baseline PARP-1 expression with respect to early treatment response (good vs. poor), ALL immunophenotype (ALL B vs. ALL T), age (children < 1 years and > 6 years vs. children 1-6 years), initial WBC (< 20 000/µl vs. ≥ 20 000/µl), and risk factor group (SR vs. IR vs. HR) were not found. PARP-1 expression was increased 12 hours after treatment in poor early treatment responders, whereas it remained statistically unchanged with respect to ALL immunophenotype, age, initial WBC, risk factor group and early treatment response. The overexpression of PARP-1 in poor early treatment responders suggests that it may contribute to treatment failure in this group of children with ALL. Our observation - if confirmed by other studies - may form the rationale for administration of PARP inhibitors in selected subsets of ALL children.

Expression of nuclear receptors (AhR, PXR, CAR) and transcription factor (Nrf2) in human parotid gland.

Nuclear receptors and transcription factors coordinate expression of many genes, and regulation of their expression determines cellular response to various endo- and exogenous factors. There is paucity of data regarding expression of nuclear receptors and factors in salivary glands. In the present study, a focus was placed on human parotid gland expression of aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR, NR1I2), constitutive androstane receptor (CAR, NR1I3) and nuclear factor E2-related factor 2 (Nrf2). Parotid salivary tissue was obtained from patients undergoing the gland dissection. Quantitative real-time PCR aimmunohistochemical staining were used for expression studies. The highest mRNA expression was documented for NFE2L2 coding for Nrf2. Lower expression was seen in the case of AHR gene coding for AhR. PXR was constitutively present at very low level and CAR expression was below the limit of quantification. Immunohistochemical evaluation of the parotid gland specimens revealed cytoplasmic Nrf2 expression in striated duct cells as well as within myoepithelial cells. Acinar cells were mostly negative for Nrf2. Expression of AhR was found within the cytoplasm in striated duct cells. Acinar and myoepithelial cells were negative for AhR. Having in mind their role in regulating function of many enzymes and transmembrane transporters, expression of these factors seem play a role in salivary gland physiology, pathology as well as drug transport and metabolism.

Endoscopic findings in the upper gastrointestinal tract in patients with Crohn's disease are common, highly specific, and associated with chronic gastritis.

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.

The Impact of Different Types of Physical Effort on the Expression of Selected Chemokine and Interleukin Receptor Genes in Peripheral Blood Cells.

This study aimed to assess the post-effort transcriptional changes of selected genes encoding receptors for chemokines and interleukins in young, physically active men to better understand the immunomodulatory effect of physical activity. The participants, aged 16-21 years, performed physical exercise tasks of either a maximal multistage 20 m shuttle-run test (beep test) or a repeated speed ability test. The expression of selected genes encoding receptors for chemokines and interleukins in nucleated peripheral blood cells was determined using RT-qPCR. Aerobic endurance activity was a positive stimulant that induced increased expression of CCR1 and CCR2 genes following lactate recovery, while the maximum expression of CCR5 was found immediately post-effort. The increase in the expression of inflammation-related genes encoding chemokine receptors triggered by aerobic effort strengthens the theory that physical effort induces sterile inflammation. Different profiles of studied chemokine receptor gene expression induced by short-term anaerobic effort suggest that not all types of physical effort activate the same immunological pathways. A significant increase in IL17RA gene expression after the beep test confirmed the hypothesis that cells expressing this receptor, including Th17 lymphocyte subsets, can be involved in the creation of an immune response after endurance efforts.

Angiogenesis within the duodenum of patients with cirrhosis is modulated by mechanosensitive Kruppel-like factor 2 and microRNA-126.

BACKGROUND: The mechanism involved in neovascularization in splanchnic circulation and the main trigger that induces angiogenesis in patients with cirrhosis are not fully recognized. AIMS: To explore the involvement of flow sensitive lung Kruppel-like factor (KLF2), microRNA-126 (miR-126), angiopoietin-2 (Ang-2) and heme oxygenase-1 (HO-1) in modulation of vascular endothelial growth factor (VEGF) signalling that have a critical effect on growth of new blood vessels. METHODS: Duodenal biopsies from 22 patients with cirrhosis and 10 controls were obtained during routine endoscopy. The process of angiogenesis was evaluated by a measurement of CD31 concentration, immunodetection of CD34 protein and estimation of capillary densities. Messenger RNA (mRNA) and protein expressions were analysed by real-time PCR, Western blot or ELISA respectively. RESULTS: Markers of angiogenesis (both, CD31 and CD34) were significantly enhanced in cirrhotic patients. In comparison to healthy controls, levels of Ang-2 and KLF-2 mRNAs as well as Ang-2, KLF-2, HO-1, VEGF protein expressions were considerably increased. Levels of sCD163, a surrogate marker of portal hypertension, correlated with levels of Ang-2, (P = 0.021) and VEGF (P = 0.009). The expression of miR-126, a KLF2-mediated regulator of the VEGF signalling was enhanced in cirrhotic patients. CONCLUSIONS: Our results demonstrate, for the first time in humans, that neovascularization is induced in duodenal tissue of patients with cirrhosis and proangiogenic factors such as KLF-2, Ang-2, miR-126 and VEGF can contribute to the angiogenesis induced by hemodynamic forces. Thus, cirrhosis-induced blood flow and pressure within splanchnic vessels may be important hemodynamic triggers that initiate the angiogenic signalling cascade.

Reed-Sternberg cells in classical Hodgkin lymphoma in children seem to be predominantly oestrogen receptor α negative and oestrogen receptor ß positive.

Oestrogen receptor α (ERα) is responsible for activation of gene transcription, while oestrogen receptor ß (ERß) serves as a negative regulator of ERα function. Since ER status is a prognostic and predictive factor in some cancers, we analysed the immunohistochemical expression of ERα and ERß in Reed-Sternberg (RS) cells in paraffin-embedded lymph node specimens from 27 children with classical Hodgkin lymphoma (HL) in relation to histological type, clinical stage, age, and gender. Percentage of RS cells with positive nuclear reaction for the presence of ERα and/or ERß was assessed. ERα positive RS cells were present in 11% (3/27) of lymph nodes (range 1-8%, mean 0.4%) whereas ERß positive RS cells were detected in 96% (26/27) of lymph nodes (range 1-97.5%, mean 61.8%). The highest percentage of ERß positive RS cells was observed in patients with the most advanced (IVB) disease as compared to patients with lower stages (90.3% vs. 56.9% respectively, p = 0.004). To the best of our knowledge this is the first report on the expression of ERß in RS cells in children. We conclude that RS cells in classical HL in children seem to be mainly ERß positive and ERα negative.

Activation of NF-ĸB in leukemic cells in response to initial prednisone therapy in children with acute lymphoblastic leukaemia: relation to other prognostic factors.

Nuclear factor ĸB (NF-ĸB) is a transcription regulator of proliferation and cell death. Increased activation of NF-ĸB may be responsible for treatment failure in children with acute lymphoblastic leukaemia (ALL). This study aimed to assess changes in NF-ĸB activation in peripheral blood mononuclear cells prior to and after 6 and 12 h of prednisone administration in relation to age, initial WBC count at diagnosis and early treatment response in childhood ALL. The study comprised 55 children with de novo ALL. Cells were stained with mouse anti-NF-ĸB (p65) antibody followed by goat anti-mouse antibody conjugated with FITC and measured by laser scanning cytometer. The nuclear/cytoplasmic (N/C) ratio of NF-ĸB reflecting activation of NF-ĸB was decreased 12 h after treatment in the standard risk group patients, whereas it remained statistically unchanged in the non-standard risk group patients. Changes in the N/C ratio of NF-ĸB were not associated with age and early treatment response; however, in children with an initial WBC count higher than 20 000/µl at diagnosis, this ratio was increased after 6 and 12 h from prednisone administration. The association of higher activation of NF-ĸB with an elevated initial WBC count suggests that activation of NF-ĸB may be responsible for treatment failure in children with ALL.

Triple negative phenomenon in endometrial cancer: recognition criteria and impact on survival.

OBJECTIVES: Endometrial cancer is the most common malignant cancer of female reproductive organs. The number of diagnosed cases of endometrial cancer is increasing from year to year. Endometrial cancer is a neoplasm with a good survival rate. However, there are also cases with a fast, aggressive course. In recent years, the triple negative phenomenon (TNP) has been identified as one of the factors determining shorter survival in patients with endometrial cancer. MATERIAL AND METHODS: The study covered 265 patients with histopathologically confirmed endometrial cancer. Patients were divided into two groups: 1) patients with endometrial cancer with TNP; 2) patients with endometrial cancer without TNP. Tissue microarrays (TMA) were examined with immunohistochemistry to evaluate the expression of estrogen, progesterone and HER2 receptors. In several cases FISH method was used to assess HER2. The expression was evaluated by computer image analysis using the Nuclear Image Analysis virtual microscopy system. The evaluation of HER2 expression was performed manually. The criterion for TNC diagnosis was H-Score < 50 or < 75 and Allred score < 4. RESULTS: Depending on the scoring system used, TNP was found in from 10.19% to 15.09% of cases. Regardless of the criteria employed in endometrial cancer, the presence of TNP was neither a factor increasing the risk of death nor it affected the patients' survival. CONCLUSIONS: The proportion of TNP diagnosed in endometrial cancer depends on the examined population and the diagnostic criteria. The incidence of TNP did not affect the survival of patients.

Endoscopic treatment of rectal neuroendocrine tumors in a 13-year retrospective single-center study: are we following the guidelines?

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 disease­free at follow­up, 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.

The gastric microbiota in patients with Crohn's disease; a preliminary study.

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.

Simultaneous assessment of p53 and MDM2 expression in leukemic cells in response to initial prednisone therapy in children with acute lymphoblastic leukemia.

Ineffective apoptosis is one of main causes of a treatment failure in childhood acute lymphoblastic leukemia (ALL). p53 plays a crucial role in triggering apoptosis of ALL in response to prednisone treatment. MDM2 is the endogenous inhibitor of apoptosis that downregulates the functional activity of p53 protein. This study is aimed to evaluate changes in MDM2 and p53 expression in peripheral blood mononuclear cells collected from children with ALL prior to and after 6 and 12 h of prednisone administration in relation to early treatment response. The study comprised 35 children with newly diagnosed ALL, subdivided into good (n = 24) and poor (n = 11) early treatment responders. MDM2 - associated APC fluorescence and p53 - associated FITC fluorescence were measured by the laser scanning cytometer. In the group of poor responders, p53 and MDM2 fluorescence were significantly higher than in the group of good responders. In the group of good early treatment responders, a statistically significant rise of p53 fluorescence measured in the nucleus and in the cytoplasm 12 h after prednisone administration as well as increase in MDM2 fluorescence measured in the cytoplasm 6 and 12 h after prednisone administration were seen. These data suggest that pretreatment overexpression of MDM2 protein may contribute to poor early treatment response.