News in gastroenterology, hepatology and digestive endoscopy.

Gastroenterology, hepatology and digestive endoscopy are rapidly evolving disciplines with significant advances in the diagnostics and treatment in the entire gastrointestinal tract. The aim of our article was to summarize new perspectives on relevant situations in gastroenterology and hepatology like acute pancreatitis, functional dyspepsia, rational indication of proton pump inhibitors, inflammatory bowel diseases (IBD), cholestatic liver diseases, alcohol induced hepatitis, non-alcoholic fatty live disease (NAFLD) and patophysiology of bilirubin and bile acids. Digestive endoscopy represents an interventional part of gastroenterology and key recent topics are mentioned like pancreatic cancer screening, arteficial intelligence, resection of low-risk neoplastic lesions, enteroscopy techniques, cholangio- and pancreatiscopy and extraluminal expansion of endoscopy techniques by means of endoscopic submucosal and transmural dissection, endoscopic myotomy and lumen apposing stents.

The effect of single and repeated doses of rivastigmine on gastric myoelectric activity in experimental pigs.

BACKGROUND: Rivastigmine is a pseudo-irreversible cholinesterase inhibitor used for therapy of Alzheimer's disease and non-Alzheimer dementia syndromes. In humans, rivastigmine can cause significant gastrointestinal side effects that can limit its clinical use. The aim of this study was to assess the impact of rivastigmine on gastric motor function by means of electrogastrography (EGG) in experimental pigs. METHODS: Six experimental adult female pigs (Sus scrofa f. domestica, hybrids of Czech White and Landrace breeds; 3-month-old; mean weight 30.7 ± 1.2 kg) were enrolled into the study twice and created two experimental groups. In group A, a single intragastric dose of 6 mg rivastigmine hydrogen tartate was administered in the morning to fasting pigs before EGG recording. In group B, rivastigmine was administered to overnight fasting animals in a dietary bolus in the morning for 7 days (6 mg per day). On day 8, an intragastric dose of 12 mg rivastigmine was given in the morning to fasting pigs before EGG. EGG recording was accomplished by means of an EGG standalone system. Recordings from both groups were evaluated in dominant frequency and EGG power (areas of amplitudes). RESULTS: In total, 1,980 one-minute EGG intervals were evaluated. In group A, basal EGG power (median 1290.5; interquartile range 736.5-2330 µV2) was significantly higher in comparison with the power of intervals T6 (882; 577-1375; p = 0.001) and T10 (992.5; 385-2859; p = 0.032). In group B, the dominant frequency increased significantly from basal values (1.97 ± 1.57 cycles per minute) to intervals T9 (3.26 ± 2.16; p < 0.001) and T10 (2.14 ± 1.16; p = 0.012), respectively. In group B, basal EGG power (median 1030.5; interquartile range 549-5093) was significantly higher in comparison with the power of intervals T7 (692.5; 434-1476; p = 0.002) and T8 (799; 435-1463 µV2; p = 0.004). CONCLUSIONS: Both single as well as repeated intragastric administration of rivastigmine hydrogen tartrate caused a significant decrease of EGG power (areas of amplitudes) in experimental pigs. EGG power may serve as an indirect indicator of gastric motor competence. These findings might provide a possible explanation of rivastigmine-associated dyspepsia in humans.

Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022.

MR1: ESGE recommends small-bowel capsule endoscopy as the first-line examination, before consideration of other endoscopic and radiological diagnostic tests for suspected small-bowel bleeding, given the excellent safety profile of capsule endoscopy, its patient tolerability, and its potential to visualize the entire small-bowel mucosa.Strong recommendation, moderate quality evidence. MR2: ESGE recommends small-bowel capsule endoscopy in patients with overt suspected small-bowel bleeding as soon as possible after the bleeding episode, ideally within 48 hours, to maximize the diagnostic and subsequent therapeutic yield.Strong recommendation, high quality evidence. MR3: ESGE does not recommend routine second-look endoscopy prior to small-bowel capsule endoscopy in patients with suspected small-bowel bleeding or iron-deficiency anemia.Strong recommendation, low quality evidence. MR4: ESGE recommends conservative management in those patients with suspected small-bowel bleeding and high quality negative small-bowel capsule endoscopy.Strong recommendation, moderate quality evidence. MR5: ESGE recommends device-assisted enteroscopy to confirm and possibly treat lesions identified by small-bowel capsule endoscopy.Strong recommendation, high quality evidence. MR6: ESGE recommends the performance of small-bowel capsule endoscopy as a first-line examination in patients with iron-deficiency anemia when small bowel evaluation is indicated.Strong recommendation, high quality evidence. MR7: ESGE recommends small-bowel capsule endoscopy in patients with suspected Crohn's disease and negative ileocolonoscopy findings as the initial diagnostic modality for investigating the small bowel, in the absence of obstructive symptoms or known bowel stenosis.Strong recommendation, high quality evidence. MR8: ESGE recommends, in patients with unremarkable or nondiagnostic findings from dedicated small-bowel cross-sectional imaging, small-bowel capsule endoscopy as a subsequent investigation if deemed likely to influence patient management.Strong recommendation, low quality evidence. MR9: ESGE recommends, in patients with established Crohn's disease, the use of a patency capsule before small-bowel capsule endoscopy to decrease the capsule retention rate.Strong recommendation, moderate quality evidence. MR10: ESGE recommends device-assisted enteroscopy (DAE) as an alternative to surgery for foreign bodies retained in the small bowel requiring retrieval in patients without acute intestinal obstruction.Strong recommendation, moderate quality evidence. MR11: ESGE recommends DAE-endoscopic retrograde cholangiopancreatography (DAE-ERCP) as a first-line endoscopic approach to treat pancreaticobiliary diseases in patients with surgically altered anatomy (except for Billroth II patients).Strong recommendation, moderate quality evidence.

Antithrombotic therapy and digestive endoscopy.

Antithrombotic therapy and digestive endoscopy Antithrombotic therapy comprises anticoagulation and antiplatelet treatment. The number of patients treated with various forms of antithrombotic therapy is growing. Procedures of digestive endoscopy are very frequently indicated by general practitioners and doctors of various specialisations. Interdisciplinary cooperation and mutual understanding are required in order for digestive endoscopy to be effective and safe. Hence, we present an overview based on recent European, British (1), and North American guidelines (2) for endoscopic procedures, with respect to guidelines for perioperative care in general (3). Antithrombotic therapy management in patients undergoing digestive endoscopy procedures is based on individual consideration of postprocedural bleeding (particularly a delayed one) on one hand, and thromboembolic risk on the other hand, ideally in cooperation with the physician prescribing antithrombotic therapy. Despite all efforts, patients taking antithrombotic medication are at a higher risk of postprocedural bleeding in comparison with those without this risk; this fact should be accepted by attending physicians and patients should be informed of it. Postprocedural bleeding is mostly manageable with a subsequent endoscopic procedure. By contrast, cerebral and cardiovascular thromboembolic complications are often life-threatening and not uncommonly disabling. One should always consider postponing an elective procedure in a patient with temporary antithrombotic therapy (after pulmonary embolism or after coronary stent insertion). Basic principles of administration of antithrombotic therapy in the context of an endoscopic procedure are described in Table 1. Digestive endoscopy procedures can be categorized according to postprocedural bleeding risk (Table 2). Postprocedural bleeding risk can be specifically reduced in some procedures (ERCP with papillary balloon dilation instead of sphincterotomy, mechanical securing of polypectomy base, etc.). Acetylsalicylic acid administered as secondary prevention (primary preventive indications are very narrow nowadays) should not be discontinued perioperatively (discontinuation is associated with an approximately threefold increase in thrombotic complications!). The riskiest procedures are the only exception in which discontinuation is explicitly requested by the digestive endoscopist. Reduction of dual antiplatelet therapy is better abandoned in high-risk patients - particularly those with recently implanted coronary stents (Table 3) - and postponement of an elective procedure should always be considered. Bridging of warfarin with low-molecular-weight heparin (LMWH) is not indicated routinely (in some cases, this practice increases the bleeding risk). Bridging with LMWH is appropriate in patients with high (or moderate) thromboembolic risk (Table 5). Furthermore, LMWH therapy carries specific risks, particularly in patients with renal function impairment (Table 4). In patients with a high thromboembolic risk, a statement of the physician indicating anticoagulation is always appropriate before an elective procedure (Table 6). Direct oral anticoagulants (DOACs) should not be administered on the day of the procedure, not even in one with a low risk (e.g., biopsy); a longer withdrawal is recommended in high-risk procedures (this cessation should not be bridged with LMWH given the rapid onset and elimination half-time) (Table 7). Recommencement of antithrombotic therapy after a high-risk endoscopic procedure should always be determined by the endoscopist and the recommended intervals should be considered minimal: 1-2 days after the procedure in the case of P2Y12 inhibitors; 2-3 days after the procedure in the case of DOACs; in the evening of the day of the procedure for warfarin with a maintenance (not saturation) dose; and 48 hours after the procedure in the case of LMWH at a therapeutic dose. Earlier administration of a lower-than-therapeutic dose of LMWH (twice a day per weight) can be considered in this context: prophylactic (once a day) or higher prophylactic (once a day per weight) doses. In general, a full anticoagulation effect should not be achieved earlier than approximately 48 hours after the procedure. The patient should be properly informed of the course of antithrombotic therapy before and after the endoscopic procedure, including a written form (a calendar can be downloaded online for this purpose).

Early gastric cancer.

Early gastric cancer is defined histopathologically as a tumour with limited local progression to the mucosa and submucosa. The concept of early cancer was developed in the 1960s in Japan and is now widely accepted. The term of early gastric cancer included cases with/without metastatic lymph node involvement. However, a common characteristic is a favourable prognosis of the disease. The task of the endoscopist is primarily to diagnose (identify) the tumour (precancerous lesions) and to verify it by biopsy. Successful identification must be followed by its correct classification, leading to the choice of an adequate approach, which includes surveillance, endoscopic treatment (resection) or surgical treatment (with or without chemotherapy). The method of treatment is determined primarily by the nature or risk of lymph node involvement.

Expression profiles of iron transport molecules along the duodenum.

Duodenal biopsies are considered a suitable source of enterocytes for studies of dietary iron absorption. However, the expression level of molecules involved in iron absorption may vary along the length of duodenum. We aimed to determine whether the expression of molecules involved in the absorption of heme and non-heme iron differs depending on the location in the duodenum. Analysis was performed with samples of duodenal biopsies from 10 individuals with normal iron metabolism. Samples were collected at the following locations: (a) immediately post-bulbar, (b) 1-2 cm below the papilla of Vater and (c) in the distal duodenum. The gene expression was analyzed at the mRNA and protein level using real-time PCR and Western blot analysis. At the mRNA level, significantly different expression of HCP1, DMT1, ferroportin and Zip8 was found at individual positions of duodenum. Position-dependent expression of other molecules, especially of FLVCR1, HMOX1 and HMOX2 was also detected but with no statistical significances. At the protein level, we observed statistically significantly decreasing expression of transporters HCP1, FLVCR1, DMT1, ferroportin, Zip14 and Zip8 with advancing positions of duodenum. Our results are consistent with a gradient of diminishing iron absorption along the duodenum for both heme and non-heme iron.

Serum Citrulline and Ornithine: Potential Markers of Coeliac Disease Activity.

INTRODUCTION: To date, there is not generally accepted and universal indicator of activity, and functional integrity of the small intestine in patients with coeliac disease. The aim of our study was to investigate whether serum concentrations of the non-essential amino acids citrulline and ornithine might have this function. METHODS: We examined serum citrulline and ornithine concentrations in a subgroup of patients with proven coeliac disease and healthy controls (blood donors). RESULTS: A total of 94 patients with coeliac disease (29 men, mean age 53 ± 18 years; 65 women, mean age 44 ± 14 years) and 35 healthy controls (blood donors) in whom coeliac disease was serologically excluded (10 men, mean age 51 ± 14 years; 25 women, mean age 46 ± 12 years) were included in the study. Significantly lower concentrations of serum ornithine were found in patients with coeliac disease (mean 65 ± 3 µmol/L; median 63 µmol/L, IQR 34 µmol/L, p < 0.001). No statistically nor clinically significant differences were found in the citrulline concentrations between the study and control group. CONCLUSIONS: Serum ornithine (but not citrulline) may be useful for assessing the functional status of the small intestine in uncomplicated coeliac disease. Further studies involving more detailed analysis of dietary and metabolic changes in patients will be needed to reach definitive conclusions.

A deep CNN model for anomaly detection and localization in wireless capsule endoscopy images.

Wireless capsule endoscopy (WCE) is one of the most efficient methods for the examination of gastrointestinal tracts. Computer-aided intelligent diagnostic tools alleviate the challenges faced during manual inspection of long WCE videos. Several approaches have been proposed in the literature for the automatic detection and localization of anomalies in WCE images. Some of them focus on specific anomalies such as bleeding, polyp, lesion, etc. However, relatively fewer generic methods have been proposed to detect all those common anomalies simultaneously. In this paper, a deep convolutional neural network (CNN) based model 'WCENet' is proposed for anomaly detection and localization in WCE images. The model works in two phases. In the first phase, a simple and efficient attention-based CNN classifies an image into one of the four categories: polyp, vascular, inflammatory, or normal. If the image is classified in one of the abnormal categories, it is processed in the second phase for the anomaly localization. Fusion of Grad-CAM++ and a custom SegNet is used for anomalous region segmentation in the abnormal image. WCENet classifier attains accuracy and area under receiver operating characteristic of 98% and 99%. The WCENet segmentation model obtains a frequency weighted intersection over union of 81%, and an average dice score of 56% on the KID dataset. WCENet outperforms nine different state-of-the-art conventional machine learning and deep learning models on the KID dataset. The proposed model demonstrates potential for clinical applications.

Dextran Sodium Sulphate-Induced Gastrointestinal Injury Further Aggravates the Impact of Galantamine on the Gastric Myoelectric Activity in Experimental Pigs.

Galantamine has been used as a treatment for Alzheimer disease. It has a unique, dual mode of action (inhibitor of acetylcholinesterase and allosteric modulator of nicotinic acetylcholine receptors). Nausea (in about 20%), vomiting (10%) and diarrhoea (5-7%) are the most common side effects. The aim of this study was to assess the effect of galantamine on porcine gastric myoelectric activity without (Group A) and with (Group B) dextran sodium sulphate (DSS)-induced gastrointestinal injury. Galantamine hydrobromide was administrated to twelve pigs as a single intragastric dose (24 mg). Gastric myoelectric activity was investigated by electrogastrography (EGG). Basal (15 min before galantamine administration) and study recordings after galantamine administration (300 min) were evaluated using a running spectral analysis. Results were expressed as dominant frequency of gastric slow waves and power analysis (areas of amplitudes). Altogether, 3780 one-minute EGG recordings were evaluated. In Group A, power was steady from basal values for 180 min, then gradually decreased till 270 min (p = 0.007). In Group B, there was a rapid gradual fall from basal values to those after 120 min (p = 0.007) till 300 min (p ˂ 0.001). In conclusion, galantamine alone revealed an unfavourable effect on porcine myoelectric activity assessed by gastric power. It can be a plausible explanation of galantamine-associated dyspepsia in humans. DSS caused further profound decrease of EGG power. That may indicate that underlying inflammatory, ischaemic or NSAIDs-induced condition of the intestine in humans can have aggravated the effect of galantamine on gastric myoelectric activity.

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) - A Helicobacter-opposite point.

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare familial gastric cancer syndrome with an autosomal dominant pattern of inheritance. It is characterised by fundic gland polyposis of the gastric body and is associated with a significant risk of gastric adenocarcinoma. Unlike sporadic gastric cancer, Helicobacter pylori is usually absent in patients with GAPPS. This opposite-point finding has so far not been fully clarified. Prophylactic total gastrectomy is indicated in all cases of GAPPS with fundic gland polyposis and the presence of any dysplasia. If no dysplasia is found at histology, prophylactic gastrectomy is suggested at between 30 and 35 years of age, or at five years earlier than the age at which the youngest family member developed gastric cancer. Different phenotypes of GAPPS demand an individual approach to particular family members.

The Impact of Dextran Sodium Sulfate-Induced Gastrointestinal Injury on the Pharmacokinetic Parameters of Donepezil and Its Active Metabolite 6-O-desmethyldonepezil, and Gastric Myoelectric Activity in Experimental Pigs.

Gastrointestinal side effects of donepezil, including dyspepsia, nausea, vomiting or diarrhea, occur in 20-30% of patients. The pathogenesis of these dysmotility associated disorders has not been fully clarified yet. Pharmacokinetic parameters of donepezil and its active metabolite 6-O-desmethyldonepezil were investigated in experimental pigs with and without small intestinal injury induced by dextran sodium sulfate (DSS). Morphological features of this injury were evaluated by a video capsule endoscopy. The effect of a single and repeated doses of donepezil on gastric myoelectric activity was assessed. Both DSS-induced small intestinal injury and prolonged small intestinal transit time caused higher plasma concentrations of donepezil in experimental pigs. This has an important implication for clinical practice in humans, with a need to reduce doses of the drug if an underlying gastrointestinal disease is present. Donepezil had an undesirable impact on porcine myoelectric activity. This effect was further aggravated by DSS-induced small intestinal injury. These findings can explain donepezil-associated dyspepsia in humans.

Mucosal healing is not associated with better outcome during 7 years of follow-up in pediatric patients with Crohn's disease.

BACKGROUND: Mucosal healing (MH) has become a perspective treatment target in patients with Crohn's disease (CD). Data about the impact of MH on long-term outcome in pediatric patients are still scarce. METHODS: 76 pediatric patients with CD were evaluated retrospectively (2000-2015) in a tertiary care center. Based on MH achievement, they were divided into two groups (MH, n= 17; and No MH, n=59). The primary endpoint was to assess the association of MH and the need for CD-related hospitalizations or surgery in pediatric patients with CD. RESULTS: The number of hospitalized patients was 24% in the MH group and 42% in the No MH group, P = 0.26. The total number of CD-related hospitalizations was not significant between the MH group and the No MH group (5 vs. 41, P = 0.15). The time to the first hospitalization was 24 months in MH and 21 months in No MH, P>0.99. 24% patients in the MH group and 39% patients in the No MH group underwent CD-related operation, P = 0.39. Time to the first operation was 43 months for MH and 19 months for the No MH group, P = 0.13. The follow-up period was 91 months in the MH group and 80 months in the No MH group, P = 0.74. The use of infliximab was positively associated with MH, P = 0.002. CONCLUSIONS: MH was not associated with fewer CD-related hospitalizations or operations in pediatric patients with CD during seven years of follow-up.

Colorectal anastomosis dehiscence: a call for more detailed morphological classification.

INTRODUCTION: A proactive approach is recommended in colorectal anastomosis leak treatment, and early diagnosis is very important. Early postoperative endoscopy would allow rapid diagnosis of anastomotic pathologies and consequent prompt intervention according to anastomotic disruption morphology. AIM: To evaluate the effectiveness of close endoscopic follow-up of all patients (including asymptomatic ones) in improving diagnosis of acute leak (AL) and reducing its complications. MATERIAL AND METHODS: This study included 124 patients who had undergone rectum resection for rectal cancer with stapled anastomosis. Endoscopy was performed between the 7th and 10th postoperative day and 1 month postoperatively. For defect morphology assessment, a classification system was created based on four levels of severity. Photographic findings were evaluated by an independent, experienced gastroenterologist. RESULTS: Postoperative endoscopy revealed 28 (22.6%) patients with acute leakage. Initial endoscopy confirmed AL in 18 patients. Six (31.6%) patients were asymptomatic and 13 (68.4%) were symptomatic. The second endoscopy revealed another 9 (32.1%) leaks (4 (44.5%) asymptomatic and 5 (55.5%) symptomatic). Sixteen (57.1%) patients had grade A leakages, 7 (25.0%) had grade B leakages, and 5 (17.9%) had grade C leakages. Furthermore, 22 of 27 (81%) defects were located posterior and posterior-laterally. Fifteen (55.5%) defects were smaller than 1/3 the circumference, 7 (25.9%) affected 1/3-1/2 of the circumference, and 5 (18.5%) affected more than 1/2 of the circumference. CONCLUSIONS: Incorporation of early endoscopy in postoperative management allows rapid diagnosis of AL and allows faster intervention, even in leaks that are clinically silent.

Peutz-Jeghers syndrome.

PURPOSE OF REVIEW: Peutz-Jeghers syndrome is a rare, autosomal dominant, hereditary polyposis syndrome defined by gastrointestinal hamartomas and mucocutaneous pigmentations, caused by a germline mutation in the serine/ threonine kinase 11 or liver kinase B1 (STK11/LKB1) genes. Hamartomatous polyps located throughout the gastrointestinal tract can be complicated by bleeding and small bowel intussusception, potentially leading to the need for emergency surgery. Individuals suffering from Peutz-Jeghers syndrome have an increased lifetime risk of various forms of cancer (gastrointestinal, pancreatic, lung, breast, uterine, ovarian and testicular). Surveillance should lead to the prevention of complications and thus a reduction in mortality and morbidity of patients. RECENT FINDINGS: A combined approach based on wireless capsule endoscopy, magnetic resonance enterography and device-assisted enteroscopy is effective in reduction of the polyp burden and thus decreasing the risk of bleeding and intussusception. Current guidelines for screening and surveillance are mostly based on expert opinion rather than evidence. SUMMARY: Peutz-Jeghers syndrome is an emerging disease that significantly affects the quality of life enjoyed by patients. Despite of all the progress in improved early diagnostics, options for advanced endoscopic therapy and elaborate surveillance, acute and chronic complications decrease the life expectancy of patients suffering from Peutz-Jeghers syndrome.

Dieulafoys jejunal lesion as a source of lifethreating bleeding.

Dieulafoy`s lesion is a rare condition characterized by bleeding into gastrointestinal tract from minimaly eroded submucous artery. Mostly is localized in stomach in elderly polymorbid men, but can occure in entire gastrointestinal tract, in both sexes, in every age. It should be thought off as one of possible causes of obscure bleeding. It is often massive, requiring fast diagnostics, treatment and multidisciplinary approach. The case report discusses patient with recurrent hemodynamicaly significant bleeding into jejunum. It pointed to combined diagnostic approach using both endoscopy and angiography. After failing endoscopically and angiografically due to hemodynamic instability, surgical intervention took place. Precise Dieulafoy`s lesion diagnosis has been determined eventually on histologic section. Diagnostic and therapeutic approach should be individual taking patient´s condition and capabilities of department into consideration. Surgical intervention remains golden standard when hemodynamic instability occures or when endoscopy and angiography fail.

Detection of abnormality in wireless capsule endoscopy images using fractal features.

One of the most recent non-invasive technologies to examine the gastrointestinal tract is wireless capsule endoscopy (WCE). As there are thousands of endoscopic images in an 8-15 h long video, an evaluator has to pay constant attention for a relatively long time (60-120 min). Therefore the possibility of the presence of pathological findings in a few images (displayed for evaluation for a few seconds only) brings a significant risk of missing the pathology with all negative consequences for the patient. Hence, manually reviewing a video to identify abnormal images is not only a tedious and time consuming task that overwhelms human attention but also is error prone. In this paper, a method is proposed for the automatic detection of abnormal WCE images. The differential box counting method is used for the extraction of fractal dimension (FD) of WCE images and the random forest based ensemble classifier is used for the identification of abnormal frames. The FD is a well-known technique for extraction of features related to texture, smoothness, and roughness. In this paper, FDs are extracted from pixel-blocks of WCE images and are fed to the classifier for identification of images with abnormalities. To determine a suitable pixel block size for FD feature extraction, various sizes of blocks are considered and are fed into six frequently used classifiers separately, and the block size of 7×7 giving the best performance is empirically determined. Further, the selection of the random forest ensemble classifier is also done using the same empirical study. Performance of the proposed method is evaluated on two datasets containing WCE frames. Results demonstrate that the proposed method outperforms some of the state-of-the-art methods with AUC of 85% and 99% on Dataset-I and Dataset-II respectively.

The pharmacokinetic parameters and the effect of a single and repeated doses of memantine on gastric myoelectric activity in experimental pigs.

BACKGROUND: Memantine, currently available for the treatment of Alzheimer's disease, is an uncompetitive antagonist of the N-methyl-D-aspartate type of glutamate receptors. Under normal physiologic conditions, these unstimulated receptor ion channels are blocked by magnesium ions, which are displaced after agonist-induced depolarization. In humans, memantine administration is associated with different gastrointestinal dysmotility side effects (vomiting, diarrhoea, constipation, motor-mediated abdominal pain), thus limiting its clinical use. Mechanism of these motility disorders has not been clarified yet. Pigs can be used in various preclinical experiments due to their relatively very similar gastrointestinal functions compared to humans. The aim of this study was to evaluate the impact of a single and repeated doses of memantine on porcine gastric myoelectric activity evaluated by means of electrogastrography (EGG). METHODS: Six adult female experimental pigs (Sus scrofa f. domestica, mean weight 41.7±5.0 kg) entered the study for two times. The first EGG was recorded after a single intragastric dose of memantine (20 mg). In the second part, EGG was accomplished after 7-day intragastric administration (20 mg per day). All EGG recordings were performed under general anaesthesia. Basal (15 minutes) and study recordings (120 minutes) were accomplished using an EGG stand (MMS, Enschede, the Netherlands). Running spectral analysis based on Fourier transform was used. Results were expressed as dominant frequency of gastric slow waves (DF) and power analysis (areas of amplitudes). RESULTS: Single dose of memantine significantly increased DF, from basic values (1.65±1.05 cycles per min.) to 2.86 cpm after 30 min. (p = 0.008), lasting till 75 min. (p = 0.014). Basal power (median 452; inter-quartile range 280-1312 µV^2) raised after 15 min. (median 827; IQR 224-2769; p = 0.386; NS), lasting next 30 min. Repetitively administrated memantine caused important gastric arrhythmia. Basal DF after single and repeated administration was not different, however, a DF increase in the second part was more prominent (up to 3.18±2.16 after 15 and 30 min., p<0.001). In comparison with a single dose, basal power was significantly higher after repetitively administrated memantine (median 3940; IQR 695-15023 µV^2; p<0.001). Next dose of 20 mg memantine in the second part induced a prominent drop of power after 15 min. (median 541; IQR 328-2280 µV^2; p<0.001), lasting till 120 min. (p<0.001). CONCLUSIONS: Both single and repeated doses of memantine increased DF. Severe gastric arrhythmia and long-lasting low power after repeated administration might explain possible gastric dysmotility side effects in the chronic use of memantine.

Non-conventional mucosal lesions (serrated epithelial change, villous hypermucinous change) are frequent in patients with inflammatory bowel disease-results of molecular and immunohistochemical single institutional study.

Chronically inflamed mucosa in inflammatory bowel disease (IBD) is associated with an increased risk of cancer. Besides IBD-associated dysplasia, there are non-conventional mucosal changes that may act as potential precursors. The aim of the study was to retrospectively review samples from IBD patients focusing on detection of such lesions with evaluation of their immunohistochemical and molecular properties. Surgical specimens and/or endoscopical biopsy samples of IBD patients examined during a 10-year period were reviewed. Detected mucosal lesions were divided into three groups-group 1 (non-conventional or putative precursor lesions - PPLs) with serrated or villous hypermucinous morphology, group 2 (true serrated polyps fulfilling valid criteria), and group 3 (IBD-associated neoplasia). Lesions from all groups were analyzed with antibodies against MLH1, p53, and MGMT and by molecular testing of KRAS, NRAS, and BRAF mutation. Samples from 309 IBD patients were reviewed. A total of 88 mucosal lesions were found in 51 patients. Most common were lesions from group 1 with superficial serrated epithelial change seen in 41 samples (46.6%) and villous hypermucinous change in 6 (6.8%). Group 2 consisted of 15 true serrated polyps. Six conventional IBD-dysplasia cases and 11 carcinomas were seen in group 3. Six lesions from group 1 were associated with invasive carcinoma whereas two shared the same mutation in KRAS or BRAF. Lesions from group 1 were characterized by loss of MGMT expression in 44.6%, aberrant p53 expression, and by mutations in KRAS gene in 42.9% of cases. This study proves the existence of mucosal changes other than conventional IBD-dysplasia and extends the knowledge about their immunohistochemical and molecular properties and relation to carcinoma further supporting their potential role in IBD-related carcinogenesis.

Accuracy of Colon Capsule Endoscopy for Colorectal Neoplasia Detection in Individuals Referred for a Screening Colonoscopy.

BACKROUND: Capsule colonoscopy might present an alternative to colonoscopy for colorectal neoplasia screening. AIM: To assess the accuracy of second-generation capsule colonoscopy (CCE2) for colorectal neoplasia detection compared with conventional colonoscopy (CC). METHODS: From 2011-2015, we performed a multicenter, prospective, cross-over study evaluating the use of CCE2 as a possible colorectal cancer (CRC) screening test based on the assessment of the method's characteristics (accuracy) and safety and patient acceptance of the routine. Enrolled participants fulfilled the CRC screening population criteria if they were asymptomatic, were older than 50, and had no personal or familial history of colorectal neoplasia. The primary outcome was accuracy for the detection of polyps ≥ 6 mm. Secondary outcomes were accuracy for all polyps, polyps ≥ 10 mm, adenomas ≥ 10 mm, and cancers, the quality of bowel cleansing, safety, and CCE2 acceptability by the screening population. RESULTS: A total of 236 individuals were examined; 11 patients (5%) were excluded. Therefore, 225 subjects (95%) were considered in the intention-to-screen (ITS) group. A total of 201 patients (89%) completed both examinations successfully (per protocol group). In the ITS group, polyps were diagnosed during CC in 114 subjects (51%); polyps ≥ 6 mm, polyps ≥ 10 mm, and adenomas ≥ 10 mm were diagnosed in 34 (15%), 16 (7%), and 11 (5%) patients, respectively. The sensitivity of CCE2 for polyps ≥ 6 mm, polyps ≥ 10 mm, and adenomas ≥ 10 mm was 79% (95% confidence interval (CI): 62-91%), 88% (95% CI: 62-98%), and 100% (95% CI: 72-100%), respectively. CONCLUSION: Second-generation capsule colonoscopy is a safe, noninvasive, and sensitive method for colorectal neoplasia detection although CC remains the preferred method for considerable proportion of subjects. CCE2 may therefore be accepted as the primary screening test for colorectal cancer screening.

Morphological, immunohistochemical and molecular features of inflammatory bowel disease associated colorectal carcinoma and associated mucosal lesions - Single institution experience.

BACKGROUND: Patients with inflammatory bowel disease (IBD) - ulcerative colitis (UC) and Crohn's disease (CD) have an elevated risk of developing colorectal carcinoma (CRC). Major risk factor in IBD patients is the continuous chronic inflammation leading to development of dysplasia and carcinoma. Nevertheless, other types of non-conventional but suspicious mucosal changes serrated change/dysplasia, NOS and villous hypermucinous change, have also been reported in IBD patients. Preneoplastic potential of these lesions is still not well elucidated. AIMS: The aim of this study was identification of IBD-associated CRCs focusing on finding related precursor lesions in the surgical specimen or in archival biopsy samples followed by a detailed morphological, immunohistochemical and molecular evaluation. For the purpose of the study the mucosal lesions were divided into conventional IBD-associated dysplasia and non-conventional lesions that were merged under a provisory term of putative preneoplastic lesions (PPL). METHODS: A total of 309 consecutive IBD colectomy specimens diagnosed during a 10-year period were reviewed. Detailed morphological evaluation, immunohistochemical analysis of mismatch repair (MMR) proteins, p53 and O6-methylguanine DNA methyltransferase (MGMT) expression and molecular analysis for KRAS, NRAS and BRAF gene mutation were performed in the retrieved CRC cases as well as in the detected dysplasia and PPLs of these patients. RESULTS: We identified 11 cases of morphologically heterogenous IBD-associated CRCs, occurring in 5 males and 6 females, aged 26-79 years (mean 44 years). A total of 22 mucosal lesions were revealed in 8 CRC patients comprising conventional IBD-associated dysplasia (4 lesions), PPLs as serrated change/dysplasia NOS (11 lesions), villous hypermucinous change (5 lesions), and two true serrated lesions (one sessile serrated adenoma and one traditional serrated adenoma). More than one type of lesion was found in 6 patients. Seven CRC cases harbored mutation of KRAS/NRAS and one case of BRAF. Two patients with KRAS-mutated CRC showed the same mutation in PPL in the same specimen (one serrated change NOS and one TSA with high-grade dysplasia). Similarly, one BRAF-mutated carcinoma case presented the same mutation in serrated change/dysplasia, NOS in the same specimen. Of the CRCs, two showed deficient MMR system profile, six presented with loss of MGMT expression, and six showed aberrant p53 expression. PPLs showed deficient MGMT expression (14 cases) and aberrant p53 (10 cases) as well. CONCLUSION: IBD-associated CRCs are very heterogeneous entities. Besides conventional IBD-related dysplasia, other types of mucosal lesions may be associated with long lasting IBD and CRC e.g. villous hypermucinous change and serrated change/dysplasia, NOS. Since these lesions share certain genetic or immunohistochemical changes with the related CRC, a suspicion is raised that these lesions may also have preneoplastic potential. Awareness of these changes is necessary to prevent their missing and under-reporting, and further studies of these lesions should be carried out.