Jiri Cyrany

Buried bumper syndrome: A complication of percutaneous endoscopic gastrostomy.

Percutaneous endoscopic gastrostomy (PEG) is a widely used method of nutrition delivery for patients with long-term insufficiency of oral intake. The PEG complication rate varies from 0.4% to 22.5% of cases, with minor complications being three times more frequent. Buried bumper syndrome (BBS) is a severe complication of this method, in which the internal fixation device migrates alongside the tract of the stoma outside the stomach. Excessive compression of tissue between the external and internal fixation device of the gastrostomy tube is considered the main etiological factor leading to BBS. Incidence of BBS is estimated at around 1% (0.3%-2.4%). Inability to insert, loss of patency and leakage around the PEG tube are considered to be a typical symptomatic triad. Gastroscopy is indicated in all cases in which BBS is suspected. The depth of disc migration in relation to the lamina muscularis propria of the stomach is critical for further therapy and can be estimated by endoscopic or transabdominal ultrasound. BBS can be complicated by gastrointestinal bleeding, perforation, peritonitis, intra-abdominal and abdominal wall abscesses, or phlegmon, and these complications can lead to fatal outcomes. The most important preventive measure is adequate positioning of the external bolster. A conservative approach should be applied only in patients with high operative risk and dismal prognosis. Choice of the method of release is based on the type of the PEG set and depth of disc migration. A disc retained inside the stomach and completely covered by the overgrowing tissue can be released using some type of endoscopic dissection technique (needle knife, argon plasma coagulation, or papillotome through the cannula). Proper patient selection and dissection of the overgrowing tissue are the major determinants for successful endoscopic therapy. A disc localized out of the stomach (lamina muscularis propria) should be treated by a surgeon.

Escherichia coli strains of phylogenetic group B2 and D and bacteriocin production are associated with advanced colorectal neoplasia

BackgroundColorectal cancer (CRC) is the 3rd most common cancer worldwide and the Czech Republic has the 6th highest incidence of CRC worldwide. Large intestinal microbiota play in its etiopathogenesis important role. Bacteriocins are proteins, produced by bacteria from the Enterobacteriaceae family. The aim of our prospective study was to assess the colonization of large intestinal mucosa by Escherichia coli strains and to investigate their bacteriocin production.MethodsA total of 30 consecutive patients with colorectal adenoma, CRA (17 men, 13 women, aged 39–79, mean age 63 ± 9), 30 patients with CRC (23 men, 7 women, aged 38–86, mean age 67 ± 11) and 20 healthy controls (9 men, 11 women, age 23–84, mean age 55 ± 15) were enrolled into prospective study. Mucosal biopsies were taken in the caecum, transverse colon and rectum during pancolonoscopy. Microbiological culture, isolation and identification of bacteria followed. Bacteriocin production was assessed by growth inhibition of indicator strains E. coli K12-Row, E. coli C6 (phi), and Shigella sonnei 17. Identification of bacteriocin-encoding determinants and E. coli phylogroups was performed using PCR methods.ResultsA total of 622 strains were isolated and further investigated. A significantly higher frequency of simultaneous production of colicins and microcins was revealed in the group of patients with CRC, when compared to patients with CRA, p = 0.031. A significantly higher frequency of E. coli phylogroup D was found in patients with CRC, when compared to controls, p = 0.044. A significantly higher prevalence of bacteriocinogeny was confirmed in patients with advanced adenoma when compared to patients with non-advanced adenoma, p = 0.010. Increasing bacteriocinogeny was associated with an increasing stage of CRC (assessed according to TNM classification). Either E. coli phylogroup B2 or E. coli phylogroup D were isolated in biopsies of patients with right-sided CRC. A statistically higher incidence of E. coli phylogroup B2 was found in patients with right-sided CRC when compared to patients with left-sided CRC, p = 0.028.ConclusionsLarge intestinal mucosa of patients with more advanced colorectal neoplasia is colonized with more virulent strains of E. coli and higher production of bacteriocins is observed in these patients when compared to those with less advanced colorectal neoplasia.

Role of S100 Proteins in Colorectal Carcinogenesis

The family of S100 proteins represents 25 relatively small (9–13 kD) calcium binding proteins. These proteins possess a broad spectrum of important intracellular and extracellular functions. Colorectal cancer is the third most common cancer in men (after lung and prostate cancer) and the second most frequent cancer in women (after breast cancer) worldwide. S100 proteins are involved in the colorectal carcinogenesis through different mechanisms: they enable proliferation, invasion, and migration of the tumour cells; furthermore, S100 proteins increase angiogenesis and activate NF-κβ signaling pathway, which plays a key role in the molecular pathogenesis especially of colitis-associated carcinoma. The expression of S100 proteins in the cancerous tissue and serum levels of S100 proteins might be used as a precise diagnostic and prognostic marker in patients with suspected or already diagnosed colorectal neoplasia. Possibly, in the future, S100 proteins will be a therapeutic target for tailored anticancer therapy.

Prevalence of hypercoagulable disorders in inflammatory bowel disease

Abstract Objective. Inflammatory bowel disease (IBD) can be associated with hypercoagulable disorders. Aim of this single-center, prospective study was an in-depth evaluation of acquired hypercoagulable states in IBD patients. Methods. A total of 110 patients with Crohns disease (CD) (aged 19–69; mean 40.5, median 38.5 years), 43 with ulcerative colitis (UC) (aged 17–72; mean 42, median 36 years), and 30 controls were enrolled. Full blood count, serum C-reactive protein (CRP), proteins C and S, activated protein C (APC) resistance, thrombin–antithrombin complex (TAT), F1+F2 fragments, tissue factor pathway inhibitor (TFPI) total and truncated, TFPI-factor Xa, tissue plasminogen activator (tPA) and PAI-I antigen were investigated in peripheral blood samples. Results. Only 18 of 153 (11.8%) IBD patients had hemocoagulation parameters within normal range. Significant difference between IBD patients and controls was found in thrombocyte volume (p < 0.001), protein C (p = 0.025), protein S (p = 0.003), APC resistance (p < 0.001), F1+F2 fragments (p < 0.001), and tPA (p = 0.002). In CD patients who were divided into two subgroups according to serum CRP values (non-active disease: <5 mg/L; active disease ≥5 mg/L), thrombocyte count was significantly lower (p = 0.001), thrombocyte volume was significantly higher (p = 0.002), F1+F2 fragments were significantly lower (p = 0.007) and tPA was significantly higher (p = 0.038) in the subgroup with CRP <5 mg/L. In UC patients, no significant difference depending on CRP was found. Conclusions. Acquired hypercoagulable abnormalities in IBD patients are frequent. Patients with active CD, but not UC, displayed significantly different hemocoagulable parameters, when compared to non-active CD/UC subjects. In patients with active CD (with increased serum CRP concentration) and patients with active extensive UC found at endoscopy (despite low CRP values), prophylactic anticoagulation therapy should be considered.

Antilaminaribioside and antichitobioside antibodies in inflammatory bowel disease

Testing antilaminaribioside (ALCA) and antichitobioside (ACCA) antibodies in 89 Crohn’s disease (CD), 31 ulcerative colitis (UC) and 50 controls, mean values were 38.6 and 53.0 ELISA units for CD, 34.0 and 32.6 for UC, 34.5 and 36.4 for controls, respectively. There was no significant difference of ALCA values between CD and UC (p = 0.401), CD and control subjects (p = 0.698) or UC and controls (p = 0.898). ACCA were significantly higher in CD compared with UC (p = 0.011) but not with the controls (p = 0.095). No significant difference of ACCA values between UC and controls (p = 0.107) was found. ALCA and ACCA values significantly correlated in CD (r = 0.548, p < 10−4) and UC (r = 0.885, p < 10−4) but not in controls (r = 0.153, p = 0.287). The positive predictive value for CD was only 20 (ALCA) and 8 % (ACCA), the negative ones (to exclude CD) 25 (ALCA) and 86 % (ACCA). Small and/or large bowel involvement or disease type (i.e. stenosing, perforating or inflammatory) of CD did not differ in the two values. The idea that ALCA and ACCA may be useful either to differentiate between CD, UC and healthy subjects or to stratify CD was not confirmed.

Pneumatosis cystoides intestinalis

RésuméLa pneumatose kystique est un état gastro-intestinal rare caractérisé par la présence de gaz dans la paroi intestinale, principalement dans celle de l’intestin grêle ou du côlon. Ce phénomène apparaît sous trois formes différentes : 1) la pneumatose kystique primaire ; 2) la forme secondaire qui accompagne un grand nombre de maladies gastrointestinales et systémiques ; 3) la pneumatose compliquant l’ischémie intestinale. La pathogénie n’est pas clairement connue, elle est très probablement multifactorielle; la surproduction d’hydrogène est la théorie la plus probable expliquant la formation de la PKI. La Pneumatose kystique intestinale (PKI) est fréquemment découverte de manière fortuite au cours d’une coloscopie — la suspicion endoscopique de la PKI, basée sur un collapse au cours de la ponction, peut être soutenue par des prélèvements cytologiques typiques. La tomodensitométrie est la technique de radiodiagnostic la plus sensible qui peut également détecter une maladie sous-jacente. L’oxygénothérapie et les antibiotiques sont essentiels dans la prise en charge conservatrice et doivent être accompagnés d’une thérapie de la maladie sous-jacente. Les candidats à une intervention chirurgicale ou radiointerventionnelle se recrutent principalement dans la troisième forme de PKI, au cours des ischémies mésentériques aiguës.AbstractPneumatosis cystoides is a rare gastrointestinal condition characterised by the presence of gas in the wall of the gastrointestinal tract, predominantly the small and large intestine. This phenomenon occurs in three forms: 1) primary pneumatosis cystoides, 2) a secondary form, which accompanies a wide range of gastrointestinal and systemic diseases, and 3) pneumatosis complicating intestinal ischaemia. The pathogenesis is not clearly known and is most likely multifactorial; hydrogen overproduction represents what is probably the most consistent theory of PCI formation. PCI is often an incidental finding during colonoscopy — endoscopic suspicion on PCI based on collapse during the puncture can be supported by the typical cytological findings. Computerised tomography is the most sensitive radiodiagnostic method, which can also detect possible underlying disease. Oxygen inhalation and antibiotics is the mainstay in conservative therapy, together with therapy of the underlying disease. Candidates for surgical and/or radiological intervention are mainly recruited from the third group of PCI accompanying abdominal catastrophe such as intestinal ischaemia.

Longitudinal molecular characterization of endoscopic specimens from colorectal lesions

AIM To compare molecular profiles of proximal colon, distal colon and rectum in large adenomas, early and late carcinomas. To assess feasibility of testing directed at molecular markers from this study in routine clinical practice. METHODS A prospective 3-year study has resulted in the acquisition of samples from 159 large adenomas and 138 carcinomas along with associated clinical parameters including localization, grade and histological type for adenomas and localization and stage for carcinomas. A complex molecular phenotyping has been performed using multiplex ligation-dependent probe amplification technique for the evaluation of CpG-island methylator phenotype (CIMP), PCR fragment analysis for detection of microsatellite instability and denaturing capillary electrophoresis for sensitive detection of somatic mutations in KRAS, BRAF, TP53 and APC genes. RESULTS Molecular types according to previously introduced Jass classification have been evaluated for large adenomas and early and late carcinomas. An increase in CIMP+ type, eventually accompanied with KRAS mutations, was notable between large adenomas and early carcinomas. As expected, the longitudinal observations revealed a correlation of the CIMP+/BRAF+ type with proximal location. CONCLUSION Prospective molecular classification of tissue specimens is feasible in routine endoscopy practice. Increased frequency of some molecular types corresponds to the developmental stages of colorectal tumors. As expected, a clear distinction is notable for tumors located in proximal colon supposedly arising from the serrated (methylation) pathway.

Abstract B09: Molecular phenotyping of colorectal tumors in clinical practice: Assignment of extended prognostic subtypes by direct testing of endoscopic specimens

Introduction: Since the pioneering work of Fearon and Vogelstein in 1990, detailed mechanisms of colorectal neoplasia have intensively been studied (1). Only recently, however, importance of molecular subtypes for prognosis has been confirmed on large cohorts (2,3). The so-called Jass classification is set to become an part of diagnostics complementary to the companion predictive genotyping (4). The diagnosis is mostly based on examination of tumor tissue from endoscopy. It was an intention of this work to evaluate feasibility of molecular phenotyping in addition to the standard testing performed from the same source material. Patients and Methods: A total of 145 carcinomas (105 fresh biopsies or 40 FFPE sections, all stages) have been acquired over a 3-year period. The molecular subtypes were assigned based upon results of CIMP/MSI/BRAF/RAS (5). To partition the most common type arising from traditional adenoma-carcinoma pathway, we have additionally examined MLH1 methylation and APC and TP53 mutations (6). The methodology was based on previously validated protocols including MS-MLPA for the evaluation of CIMP, PCR fragment analysis MSI and high-sensitive denaturing CE assay (DCE) for somatic mutations in RAS, BRAF, TP53 and APC genes. By extending Jass classification we recognize 6 molecular subtypes with distinct features: CIMP status > negative > TP53 > positive > Traditional CIMP (median prognosis) > positive > MLH1 ------------> negative > KRAS -----------------------> positive > Traditional CIN antiEGFR resistant (median prognosis) -----------------------> negative > APC> positive > Traditional CIN antiEGFR sensitive (median prognosis) ------------> positive > BRAF --------------------> negative> MSI > positive > Familial MSI (good prognosis) --------------------> positive > MSI --------------------------------> negative > Serrated CIMP (poor prognosis) --------------------------------> positive> Serrated CIMP+MSI (best prognosis) Results: A total of 105/105 (100%) of fresh tissue samples and 33/45 (73.3%) of FFPE samples provided high-quality DNA for subsequent completion of the complete molecular testing panel. The distribution of the six types was (i) 3x Serrated CIMP (ii) 9x Serrated CIMP+MSI; (iii) 2x Familial MSI, (iv) 26x Traditional CIN antiEGFR resistant (v) 12x Traditional CIN antiEGFR sensitive and (vi) 18x Traditional CIMP. The remaining 68 carcinomas were resulting from other combinations. Conclusions: Methodology as well as logistics of sample processing has been optimized for use at endoscopy unit. The distribution of Jass molecular subtypes corresponded to the larger foreign cohorts with the dominating contribution from the Traditional CIN/CIMP subtypes. Until CIMP/CIN/MSI panels covering all markers have been developed a multi-tier testing according to the above algorithm is the most cost efficient. Assignment of molecular subtypes by an optimized protocol is useable in clinical management of patients and feasible in routine practice. Supported by IGA Ministry of Health project No. NT 14383 Literature 1. Fearon ER, Vogelstein B. Cell. 1990 Jun 1;61(5):759-67. 2. Phipps AI et al. Gastroenterology 2015; 148: 77-87.e2 3. Sinicrope FA et al. Gastroenterology 2015; 148: 88-99. 4. Modest DP et al. Ann Oncol. 2016 Jun 29. pii: mdw261. [Epub ahead of print] 5. Jass JR. Int J Colorectal Dis 1999; 14: 194-200 6. Kim JH, Bae JM, Cho NY, Kang GH. Oncotarget 2016; Epub ahead of print Citation Format: Marek Minarik, Tereza Halkova, Petra Minarikova, Barbora Belsanova, Stepan Suchanek, Jiri Cyrany, Jan Bures, Miroslav Zavoral, Lucie Benesova. Molecular phenotyping of colorectal tumors in clinical practice: Assignment of extended prognostic subtypes by direct testing of endoscopic specimens. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B09.