Microsatellite instability in metaplasia-dysplasia-adenocarcinoma sequence of Barrett esophagus: a retrospective study.

AIM: To analyze the loss of mismatch repair (MMR) system protein expression in metaplasia-dysplasia-adenocarcinoma sequence of Barrett esophagus (BE). METHODS: This study retrospectively analyzed the data from 70 patients with pathohistological diagnosis of BE or esophageal adenocarcinoma (EAC) treated at the Clinical Department of Pathology and Cytology, University Hospital Center Zagreb, from January 2009 to January 2011. Patients were divided into three groups: BE without dysplasia (22 patients), BE with dysplasia (37 patients), and EAC (11 patients). Immunohistochemical expression of MutL homologue 1 (MLH1), MutS homologue 2 (MSH2), postmeiotic segregation increased 2 (PMS2), and MutS homologue 6 (MSH6) of DNA MMR system was measured and compared with tumor protein p53 expression. RESULTS: A total of 81.8% and 81.8% patients with EAC, 32.4% and 35.1% patients with dysplasia, and 50% and 54.5% patients without dysplasia had loss of MLH1 and PMS2 expression, respectively. Patients with EAC and patients with dysplasia did not have loss of MSH2 and MSH6 expression, and 18.2% patients without dysplasia had loss of MSH2 and MSH6 expression. There was a strong positive correlation between MLH1 and PMS2 expression (Spearman ρ 0.97; P<0.001) and between MSH2 and MSH6 expression (Spearman ρ 0.90, P<0.001) in the entire sample and in all BE groups. No significant correlations of MLH1 and PMS2 with p53 expression were found, except in dysplasia group (φ 0.402, P=0.030 for MSH1; φ 0.371, P=0.042 for PMS2). CONCLUSION: Although we demonstrated considerable loss of MLH1 and PMS2 expression in BE-associated carcinoma sequence, due to the retrospective study design and low number of patients we cannot conclude that MLH1 and PMS2 can be used as biomarkers for patient surveillance and therapy-making decisions. Oxford Centre for Evidence-based Medicine level of evidence: 3.

THE OVER-THE-SCOPE-CLIP FOR THE TREATMENT OF THE DIGESTIVE TUBE LEAKS AND TEARS: A CASE-SERIES. / LIJECENJE OSTECENJA PROBAVNE CIJEVI PRIMJENOM ENDOSKOPSKE STEZALJKE: PRIKAZ SERIJE BOLESNIKA.

Digestive tube damages represent a therapeutic challenge for the gastrointestinal endoscopists. Recenty, a novel device ­ the-over-the-scope clip (OTSC) ­ has been introduced for non-surgical treatment of gastrointestinal perforations, fi stula, anastomotic leaks and refractory gastrointestinal bleeds. This study aimed to evaluate the therapeutic effi cacy of OTSC in our case series. A total of nine patients were included (six males, medain age 72 years, range 58-86). The indications were upper gastrointestinal bleeding (refractory to standard endoscopic treatment: fi ve patients, a vessel with a large caliber: one patient), fi stula in two patients, and iatrogenic perforation of the sigmoid colon in one patient. Atraumatic and traumatic versions of OTSCs with twin graspers were used. All of the patients were treated with only one OTSC, and none of the patients required additional endoscopic treatment. The OTSC procedure had 100% technical success. In a subgroup of patients with perforation and fi stulae, the clinical success was 67%, whereas in those with the bleedings it was 50%. The median follow-up was 34 days (range: 3-452). OTSC is a safe and effective device for closure of perforations and leaks. However therapeutic effi cacy was subopimal in patients with the upper gastrointestinal bleedings possibly due to the application of the sharp-teeth OTSC.

[Croatian guidelines for diagnostics and treatments of Helicobacter pylori infection]. / Hrvatski postupnik za dijagnostiku i terapiju infekcije Helicobacterom pylori.

In the past 30-year period of investigations, the crucial role of Helicobacter pylori in chronic gastritis, gastric and duodenal ulcer development, and subsequently in gastric cancer and MALT lymphoma pathogenesis, has been recognized. During the first meeting of European Helicobacter Study Group in 1996 in Maastricht, the first recommendations for diagnostics and treatments of Helicobacter pylori infection were published, later reviewed in 2000, 2007 and 2010. The first meeting of Croatian doctors focusing on the same topics, but suitable to specific national circumstances, was held as early as 1998. The need for updating the old guidelines has emerged during the last years. The working expert group of gastroenterologists was formed and gathered on Consesus Conference in December 2012 in Zagreb, to arrive to current guidelines for the clinical management of Helicobacter pylori infection in Croatia. The following topics relating to Helicobacter pylori infection were examined: 1. indications and contraindications for diagnostics and treatments; 2. diagnostic methods and 3. treatments applicable in our country.

[Breast cancer metastases to the stomach and colon: two case reports]. / Metastaze karcinoma dojke u zeludac i debelo crijevo: prikaz dviju bolesnica.

Summary. Breast cancer has a high potential for metastasis, usually to the lungs, bones, liver and lymph nodes. Metastases in the holow organs of the digestive system are rare and mainly affectes the stomach and colon. They are characterized by very different clinical and radiological manifestations. We have warned that the initial unrecognized breast cancer can appear as a primary tumor of the stomach and colon, and onlya histopathological analysis reveales that it is a metastatic breast cancer. Metastases to the stomach or intestine involve deep layer of the mucosa and pathohistological findings of standard biopsy sample can be falsely negative, despite positive imaging technique (abdominal ultrasound and MSCT, endoscopic ultrasound) that indicate the tumor process. That's,why we emphasize the importance of endoscopic mucosal resection in the detection of malignant process of deeper layers of the gastric mucosa and deep intestinal mucosal biopsies with postoperative analysis of its walls.

[Intraductal papillary mucinous neoplasm of the pancreas: case report and review of the literature]. / Intraduktalna papilarna mucinozna novotvorina gusterace: prikaz slucaja i pregled literature.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a relatively rare clinical entity with a main characteristic being mucus production. Extension of IPMN along pancretic ducts and mucus production lead to ductal obstruction and dilatation, resulting in recurrent episodes of acute pancreatitis. Molecular background of IPMN-a comprises several aberrations, with the K-ras gene mutation being the likely trigger that initiates further genetic changes. Due to its indolent nature, IPMN is most commonly diagnosed in the 7th decade of life. Depending on the histology type, IPMN has a malignant potential. Therefore, surgical therapy remains a "gold standard" of treatment. Insidious, slow progression of the disease and absence of symptoms in a certain number of patients makes diagnostic approach to this entity difficult. In this paper we present a patient with IPMN of the pancreas, in whom the episodes of acute pancreatitis had been present for 22 years.

[Endoscopic mucosal resection of sessile polypoid colorectal lesions: a two-year retrospective study, technique description, indications and complications]. / Endoskopska mukozna resekcija sesilnih polipoidnih lezija debelog crijeva: dvogodisnja retrospektivna analiza, prikaz tehnike, indikacija i komplikacija.

INTRODUCTION: Endoscopic mucosal resection (EMR) is a therapeutic method for removal of sesile premalignant lesions and intramucosal carcinoma of the gastrointestinal tract. No reports on EMR data in Croatia have been published yet. MATERIALS AND METHODS: All patients included in the study were managed at the University Hospital Centre Zagreb between December 2006 and December 2008. EMR was performed using strip technique with submucosal injection of epinephrine (dilution with saline 1:5000-10000). RESULTS: EMR of sessile polypoid colorectal lesions was performed in 95 patients. The most common localisation of the disease was rectum (52 pts - 54.7%). In most patient size of the lesion was between 16-25 mm (43 pts - 45%). En-bloc resection was performed in 75 patients and piecemeal resection in the rest. Bleeding occurred immediately during the EMR in 5 pts (5.3%). Patohistological diagnosis revealed tubulovillous adenoma in 67 pts (70%). Invasive carcinoma was observed in 6 pts (6.3%) and intramucosal carcinoma in 20 pts (21%). On follow up, 73 pts (77%) did not show and sign of disease recurrence. Surgery was needed in 6 pts (6.3%) due to the diagnosis of invasive carcinoma. CONCLUSION: EMR is safe and reliable method with low risk of serious complications and acceptable recurrence rate.

Endoscopic ultrasound elastography as a method for screening the patients with suspected primary sclerosing cholangitis.

OBJECTIVES: Currently, magnetic resonance cholangiography is being used for establishing the diagnosis of primary sclerosing cholangitis, whereas endoscopic retrograde cholangiography is reserved for therapeutic interventions. The aim of this study was to determine the role of endoscopic ultrasound elastography in the detection of inflammatory and fibrotic lesions of the common bile duct. METHODS: Linear endoscopic ultrasound elastography of the common bile duct was performed in 41 patients. The patients were divided into two groups: disease group (20 patients with both, primary sclerosing cholangitis and inflammatory bowel disease) and control group (21 patients). Main outcome measurements were diameter, wall thickness and wall qualitative Elasto Score of the common bile duct. RESULTS: The disease group consisted of nine females and 11 males, whereas the control group consisted of 13 females and eight males, with no sex differences observed (chi = 0.6, d.f. = 1, P = 0.443). There was no significant difference in the diameter of common bile duct between the studied groups: 4.67+/-1.83 mm in the disease group and 5.88+/-2.47 mm in controls (t = -1.77, d.f. = 39, P = 0.085). Hard or mixed Elasto Score was found in 16 patients and four controls, being significantly different compared with the soft Elasto Score found in four patients and 17 controls (chi = 1.8, d.f. = 1, P<0.001). A significant difference was observed in the common bile duct wall thickness: 0.89+/-0.59 mm in the disease group and 0.39+/-0.14 mm in controls (t = 3.75, d.f. = 39, P<0.001). CONCLUSION: Endoscopic ultrasound elastography might be a useful noninvasive method in diagnosing primary sclerosing cholangitis.

[Narrow band imaging: new paradigm in gastrointestinal video-endoscopy]. / Prikaz uskim spektrom: nova paradigma u gastrointestinalnoj videoendoskopiji.

Novel technologies in gastrointestinal endoscopy, such as magnification and high resolution endoscopy, have a clear aim in improving diagnostic accuracy of mucosal abnormalities. Narrow band imaging encompasses both of these by endoscopic display of gastric mucosa with bands of blue and green light. This enhances mucosal architecture and adjacent vasculature. Combined with optical magnification NBI enables recognition of subtle mucosal abnormalities, such as dysplasia in Barrett's oesophagus, early morphological changes of vasculature in inflammatory and malignant diseases of esophagus, stomach and colon. Before NBI becomes a routine diagnostic procedure, further investigations are needed especially in regard to standardisation and validation of findings, as well as their correlation with histopathological findings.

[Pseudocysto-gastrostomy guided by endoscopic ultrasound---new approach to old therapeutic problem]. / Pseudocistogastrostomija vodena endoskopskim ultrazvukom--novi pristup starom terapijskom problemu.

It has been appreciated for a long time that surgery is the treatment of choice for pancreatic pseudocysts. Endoscopic internal drainage is an alternative to surgical intervention, but requires bulging of pseudocyst in gastric lumen and carries the risk of bleeding from gastric vessels. Endosonographically guided pseudocyst drainage, an elegant one-step method to connect gastric lumen with pseudocyst avoiding the risk of bleeding using EUS guidance and Doppler is described with review of literature. The procedure was for the first time successfully performed in Croatia.

The aer-o-scope: proof of concept of a pneumatic, skill-independent, self-propelling, self-navigating colonoscope.

BACKGROUND & AIMS: Endoscopic screening of the colon with available instruments requires considerable training, is often painful, and carries a risk of perforation. New instrument platforms for endoscopic screening could be useful. The aim of this study was to evaluate the extent of colonic intubation by using a novel self-propelled, self-navigating endoscope (the Aer-O-Scope; GI View Ltd, Ramat Gan, Israel). METHODS: Twelve young healthy volunteers underwent complete bowel preparation followed by a nonsedated examination using the novel device. Each examination was followed by a standard colonoscopy for safety evaluation. Cecal intubation was confirmed by endoscopic landmarks and fluoroscopy. RESULTS: In 10 out of 12 subjects (83%) the cecum was successfully reached, whereas in 2 cases the Aer-O-Scope advanced to the hepatic flexure. The time to complete advancement to cecum averaged 14.0 +/- 7 minutes, and the driving pressures averaged 34 +/- 2.3 milibar. Two subjects requested analgesics during the procedures (in both cases the cecum was reached). Four subjects experienced sweating and a bloating sensation that resolved spontaneously. All subjects were followed up to 48 hours and then for 30 days postprocedure, and no complications were observed. CONCLUSIONS: In a preliminary pilot feasibility study of this new instrument, the Aer-O-Scope effectively intubated all or most of the colon. Further clinical studies are warranted.

Color Doppler ultrasonography is reliable in assessing the risk of esophageal variceal bleeding in patients with liver cirrhosis.

PURPOSE: The aim of the study was to examine the role of Doppler ultrasonography of the portal vein in predicting esophageal variceal bleeding in patients with liver cirrhosis and portal hypertension by comparing the ultrasound data to the endoscopic findings. PATIENTS AND METHODS: 99 patients with liver cirrhosis and esophageal varices underwent color Doppler ultrasonography and esophagogastroduodenoscopy. The following portal hemodynamic parameters were analyzed: diameter and cross-sectional area, mean blood flow velocity, blood flow volume, perfusion pressure gradient, congestion index, and platelet count-to-spleen diameter ratio. Variceal characteristics, the size and the presence of red signs, were determined by endoscopic examination. RESULTS: Patients with variceal red signs had significantly higher values of portal diameter (1.538 +/- 0.246 vs. 1.243 +/- 0.167), cross-sectional area (1.286 +/- 0.448 vs. 0.945 +/- 0.256), blood flow volume (965.520 +/- 432.728 vs. 625.117 +/- 320.999) and congestion index (0.165 +/- 0.068 vs. 0.126 +/- 0.051) than patients without red signs, while the perfusion pressure gradient (0.260 +/- 0.087 vs. 0.447 +/- 0.271) and the platelet-to-spleen ratio (522.424 +/- 222.823 vs. 708.921 +/- 230.769) were lower. The same pattern of differences between the ultrasound parameters was found in patients with large varices comparing ones with red signs to the ones without them (diameter, 1.567 +/- 0.234 vs. 1.258 +/- 0.175; cross-section, 1.313 +/- 0.455 vs. 1.061 +/- 0.264; flow volume, 988.195 +/- 443.353 vs. 739.423 +/- 414.281; congestion index, 0.171 +/- 0.067 vs. 0.130 +/- 0.058; perfusion pressure gradient 0.247 +/- 0.078 vs. 0.501 +/- 0.379 and platelet-to-spleen ratio 479.930 +/- 184.302 vs. 699.094 +/- 316.171). Differences in values of ultrasonographic parameters were less obvious among groups of patients with different variceal sizes: only the diameter, cross-sectional area and blood flow volume were significantly different. The mean blood flow velocity did not depend on the variceal size or on the presence of red signs. The sensitivities and specificities of the analyzed parameters were 60-80% and 48.6-78.4%, respectively. CONCLUSIONS: Results suggest that color Doppler ultrasonography is a useful noninvasive method for evaluating the risk of esophageal variceal bleeding in patients with liver cirrhosis.

Palliative treatment of hepatocellular carcinoma with percutaneous ethanol injection using tumor's feeding artery occlusion under the ultrasonic color Doppler guidance.

We evaluate the efficacy of PEIT in patients with HCC using duplex color Doppler US. The study included 27 HCC patients admitted to the University Hospital Centre Zagreb, between 1993 and 1997. PEIT was performed for ablation of tumor supplying vessels in HCCs of < 5 cm in diameter, and as a palliative measure for tumor feeding vessel obliteration in larger tumors. The efficacy of PEIT was evaluated with duplex color Doppler US, and controlled by dynamic CT scan (16 patients) or selective angiography of hepatic artery (11 patients). All patients had well vascularized tumors before PEIT, and after therapy 25 of them showed absent or minimal tumor vascularization. Recanalization of the tumor feeding vessel was detected with Doppler US within 9 months after therapy. Study results suggested that duplex color Doppler US should be the method of choice in the evaluation of PEIT as well as in the follow-up of HCC patients after PEIT.

[Linear endoscopic ultrasound in the diagnosis of diseases of the digestive system]. / Linearni endoskopski ultrazvuk u dijagnostici bolesti probavnog sustava.

This article reviews the recent literature on the role of endoscopic ultrasonography (EUS) as diagnostic and therapeutic tool, defines it's place in the algorithm of diagnostic procedures and informs how to treat gastroenterologic patients evaluated by EUS. Endoscopic ultrasonography utilizes the technology of endoscopy to introduce high-frequency ultrasound probes in the upper or lower part of gastrointestinal tract to visualize gastrointestinal wall and adjacent structures. Longitudinal endoscopic probe is different, compared to radial probe, and advantage is use of Doppler technique. This method has came out as an important modality for the diagnosis and staging of benign and malignant lesions of the gut wall and surrounding structures of the mediastinum, abdomen and pelvis. It is also used as a diagnostic tool for the evaluation of submucosal masses of the upper gastrointestinal tract and the rectosigmoid, for locating pancreatic endocrine tumors, and for the assessment of vascular disease. The widest application of EUS is, however, in the diagnosis and staging of esophageal, gastric, rectal, and pancreaticobiliary carcinoma. EUS has been shown to change the approach to clinical management in a significant proportion of patients to a less costly, risky, or invasive strategy.

[First online continuing tele-education in gastroenterology in Croatia]. / Prva "on-line" trajna teleedukacija iz gastroenterologije u Hrvatskoj.

The expansion and popularity of the Internet created the expansion of tele-medicine, with tele-education as its important part. Such on-line distance learning is especially important for diseases being in the focus of public health interest, as diseases of the gastrointestinal, hepatobiliary and pancreatic system due to their frequency. Therefore, in this study is shown the "TIGEL project of tele-interventional gastroenterology" that was launched in May 2001 at the Center for Interventional Gastroenterology, Department of Gastroenterology, University Department of Medicine, Zagreb University Hospital Center. The project includes creation of a web site at the server of the Zagreb University School of Medicine (www.mef.hr/edumed/gastro/index.html), and among the most important goals of the project is continuous medical tele-education in gastroenterology. Beside description of the project, one of the founders of continuous on-line medical education in Croatia, this work describes many advantages but also some still unsolved questions considering medical tele-education, a very promising but still developing way of education.

[Percutaneous endoscopic gastrostomy: 5-year experience at out center (1997-2002)]. / Perkutana endoskopska gastrostomija: petogodisnje iskustvo naseg centra (1997-2002).

Gauderer and Ponsky first described percutaneous endoscopic gastrostomy (PEG) in 1979. It was introduced as a routine method in the Division of Gastroenterology, University Hospital Rebro, Zagreb, in 1995. Over the years the number of PEG insertions has increased significantly. We reviewed the available literature and compared the results with our experience according to indications, complications and efficacy of the procedure. We inserted PEG in 86 patients from January 1, 1997 until January 31, 2002. There were 40 females and 46 males. The most frequent indication for PEG insertion was a neurological condition (60/86). There were no deaths directly related to the procedure. One patient had a leakage of PEG feeding into the peritoneal cavity that caused severe peritonitis and required urgent laparatomy within 24 hours of the PEG insertion. Two patients had local infection and the tube had to be removed. The antibiotic prophylaxis has been given to 65 patients. Our experience confirms that PEG is a relatively safe and well tolerated procedure.

Surgical resection in the treatment of primary gastrointestinal non-Hodgkin's lymphoma: retrospective study.

AIM: To evaluate the role of surgical resection in the treatment of patients with primary gastrointestinal non-Hodgkin s lymphoma in our institution. METHOD: The retrospective study included 79 patients with a histologically confirmed primary gastrointestinal lymphoma, who were diagnosed and treated for the disease in the 1978-1997 period. According to the treatment modality, the patients were divided into surgically treated and surgically non-treated group. Data were analyzed with Fisher s exact test, long-rank test, and Kaplan-Meier method. RESULTS: The stomach was the primary site of non-Hodgkin s lymphoma in 45 (57%) patients, small intestine in 19 (24%), and colon in 9 (11%) patients. Six patients (8%) had multifocal disease. There were 56 (71%) patients with stages IE and IIE, and 23 (29%) with stages III and IV. Aggressive histology was found in 51 cases (65%), and low grade mucosa-associated lymphoid tissue (MALT) lymphoma in 28 (35%). Helicobacter pylori infection was registered in 20 out of 45 patients with gastric lymphoma. Twenty-six (33%) patients underwent surgical resection followed by chemotherapy, 47 (59%) were treated with chemotherapy alone, and 6 (8%) received antibiotics plus chemotherapy. Fifteen patients needed urgent surgical intervention. The overall response rate was 77%. Complete remission was achieved in 54 (68%) patients and partial remission in 7 (9%). Eighteen patients (23%) experienced progressive disease. A 10-year overall survival (OS) was 63% and event-free survival (EFS) was 52% for all patients. Patients with gastric lymphoma had better OS and EFS than patients with primary lymphoma at other sites (65% vs 42%, and 62 vs 28%, respectively) (p=0.005). A 10-year EFS rates were 58% and 52% for surgically treated and non-treated group, respectively. There was no significant difference between patients with resected and non-resected tumors (p=0.855). Patients with early-stage disease had significantly better OS and PFS than patients with advanced-stage disease (p=0.048). CONCLUSION: Primary gastrointestinal lymphoma can be successfully treated with chemotherapy alone but surgery remains an important therapeutic option for emergency problems. The main prognostic factors were primary tumor site and extent of the disease.

[Importance of the Barrett esophagus in the development of esophageal adenocarcinoma]. / Vaznost Barrettova jednjaka u nastanku adenokarcinoma jednjaka.

Arising of esophageal carcinoma, particularly adenocarcinoma of esophagus could be prevented. With correct nutrition, avoiding of substances which could lead to carcinogenesis patients could help himself in esophageal carcinoma prevention. Thats for, broad education of population on state level is needed. Duly discovering and treatment of reflux disease is a key factor in preventing of complications, especially Barretts esophagus which is premalignant lesion by itself. Program of long term endoscopic and histology follow up contribute in esophageal adenocarcinoma prevention or its early discovering in a stage of curability.