THE CONCENTRATION OF INTERLEUKIN 6 AND TUMOR NECROSIS FACTOR ALPHA IN SALIVA AND BLOOD OF PATIENTS WITH INACTIVE MULTIPLE SCLEROSIS AND COEXISTING HASHIMOTO'S THYROIDITIS.

The concentration of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the blood is higher in patients with active multiple sclerosis (MS) compared to those with inactive disease. The concentration of IL-6 and TNF-α in the blood is higher in patients with Hashimoto's thyroiditis (HT) compared to those with a healthy thyroid. The aim of the study was to assess whether serum IL-6 and TNF-α levels correlated with saliva in patients with inactive MS and whether there was a difference in these groups of patients depending of thyroid status. We also examined the correlation of thyroid stimulating hormone (TSH) levels with thyroid status. The study included 54 patients in the inactive phase of MS. The level of cytokines in the blood was determined by chemiluminescence, and in saliva by ELISA. Blood and saliva IL-6 levels showed positive correlation, while blood and saliva TNF-α levels were not correlated. There was a significantly higher TSH level in patients with inactive MS with positive thyroid antibodies, without therapy, compared with those with negative antibodies.

A Single Small Bowel Hemangioma Detected by Video Capsule Endoscopy in a Patient Presenting with Iron-deficiency Anemia - Two Case Reports.

Hemangioma of the small intestine is a rare vascular malformation which mostly presents as occult gastrointestinal bleeding and iron-deficiency anemia. Patients are often asymptomatic except of fatigue due to anemia. Hemangiomas can arise anywhere in the luminal gastrointestinal tract, with jejunum as the most commonly involved site. They are very hard to recognize mostly due to their localization. Video capsule endoscopy and balloon-assisted enteroscopy have very much improved preoperative diagnostics and made major contribution to establishing the diagnosis - which was very difficult in the past and almost all cases were diagnosed during or after the operation. Surgical resection is still the conventional treatment modality, although with the improvement of endoscopic therapeutic interventions (endoscopic mucosal resection, argon-plasma coagulation) there are more therapeutic possibilities.

LEUKOCYTAPHERESIS IN THE MANAGEMENT OF SEVERE STEROID-DEPENDENT ULCERATIVE COLITIS.

Ulcerative colitis (UC) is a multifactorial disease of unknown precise etiology and immunopathogenesis. Peripheral blood granulocytes and monocytes/macrophages are the major sources of cytokines, which regulate inflammation. Leukocytapheresis (LCAP) is a method where blood is processed by apheresis system that removes lymphocytes and plasma before being returned to the body. We report the first case in Croatia where we used LCAP in the treatment of a patient with severe steroid-dependent UC. After 12 LCAP procedures, good clinical response was obtained and there were no significant adverse side effects noticed. The patient remained in clinical remission over two years in which he underwent regular follow ups at outpatient clinic. Over a 10-year follow-up period after LCAP, the patient had only occasional clinical symptoms of disease activity. The clinical course was complicated with the development of metastatic colorectal carcinoma, which points to the importance of regular disease monitoring rather than the increased risk of malignant disease after LCAP. Patients with UC are a demanding group of patients that warrant the search for novel treatment strategies other than conventional pharmacological therapies. Although LCAP is still not a common treatment modality in our daily practice, data from recent studies suggest it to be an effective and safe procedure in the management of active UC patients.

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.

[PREDICTORS OF POOR BOWEL PREPARATION FOR COLONOSCOPY: A SINGLE-CENTRE PROSPECTIVE STUDY]. / PRETKAZATELJI LOSE PRIPREME BOLESNIKA ZA KOLONOSKOPIJU: MONOCENTRICNO PROSPEKTIVNO ISPITIVANJE.

Adequate bowel preparation is the key of a successful colonoscopy. The aim of the study was to analyze sociodemographic and clinical characteristics in our population of patients referred for colonoscopy. Bowel cleanness was evaluated using the Boston Bowel Preparation Scale (BBPS) where values 7 were considered a criterion of successful bowel preparation. The study involved 286 subjects (61.5% male, median 61 years, interquartile range 50-71). BBPS score 7 was found in 145 subjects (50.7%). Multivariate analysis indicated that subjects with severe comorbidity (ASA status 3, OR = 0,29; 95% CI: 0.12-0.72; p = 0,008) represented a risk factor for poor bowel preparation. Regimens with polyethyleneglycol (PEG) were superior compared with other protocols (OR = 2.54; 95% CI: 1.27-5.10; p = 0.008). Timing of the colonoscopy also contributed to better bowel preparation (OR = 5.50; 95% CI: 2.07-14.67; p = 0.001). This study confirms that presence of comorbidity and non-use of PEG regimens are predictors of poor bowel preparation in our population of patients referred for colonoscopy.

[Clinical characteristics of patients with a double pylori]. / Klinicke karakteristike bolesnika s dvostrukim pilorusom.

Double pylorus (DP), is a form of gastroduodenal fistula, which consists of a short accessory canal from the gastic antrum to the duodenal bulb, and mostly occrus in the background of peptic ulcer disease. Prevalence, as well long-term follow-up of patients with DP is less elucidated in western countries. Aim of our study was to analyse demografic, clinical and endoscopic characteristics in our case-series. During 2008-2013. a total of 23836 upper endoscopies were performed in 16759 patients. DP was diagnosed in 6 patients (prevalence of 0.04%). The follow-up period was f 8 to 72 months. In 87% DP was a complication of the upper gastrointestinal bleeding. In 83% cases opening of the fistula was on lesser curvature of gastric antrumu. During follow-up period the fistula healing did not occur in any of our patients. DP is a very rare entity, with a benign course of the disease Associated comorbidity and use of ulceriform medications plays important role in persistence of DP, wheras possible eradication of Helicobacter infection in this background remains elusive.

MDR1 polymorphisms are associated with inflammatory bowel disease in a cohort of Croatian IBD patients.

BACKGROUND: Inflammatory bowel diseases (IBD) are chronic diseases of unknown etiology and pathogenesis in which genetic factors contribute to development of disease. MDR1/ABCB1 is an interesting candidate gene for IBD. The role of two single nucleotide polymorphisms, C3435T and G2677T remains unclear due to contradictory results of current studies. Thus, the aims of this research were to investigate the association of MDR1 polymorphisms, C3435T and G2677T, and IBD. METHODS: A total of 310 IBD patients, 199 Crohn's disease (CD) patients and 109 ulcerative colitis (UC) patients, and 120 healthy controls were included in the study. All subjects were genotyped for G2677T/A and C3435T polymorphism using RT-PCR. In IBD patients, review of medical records was performed and patients were phenotyped according to the Montreal classification. RESULTS: Significantly higher frequency of 2677T allele (p=0.05; OR 1.46, 95% CI (1.0-2.14)) and of the 3435TT genotype was observed among UC patients compared to controls (p=0.02; OR 2.12; 95% CI (1.11-4.03). Heterozygous carriers for C3435T were significantly less likely to have CD (p=0.02; OR 0.58, 95% CI (0.36-0.91)). Haplotype analysis revealed that carriers of 3435T/2677T haplotype had a significantly higher risk of having UC (p=0.02; OR 1.55; 95% CI (1.06-2.28)). CONCLUSION: MDR1 polymorphisms are associated with both CD and UC with a stronger association with UC.

[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.

Self-expandable metal stent for dysphagia caused by mediastinal masses in patients with lung cancer.

BACKGROUND AND STUDY AIMS: We intended to evaluate the role of self-expandable metal stents (SEMS) for palliation of malignant dysphagia in patients with lung cancer. PATIENTS AND METHODS: During the period between May 2015 and September 2017, 42 SEMS have been placed for malignant dysphagia in patients with lung cancer. Stents have been placed under combined fluoroscopic and endoscopic guidance. RESULTS: Data from 42 patient were analysed. 35 patients (83%) were males and the mean age was 68,4 years (range 52-80 y). In 26 patients (61%) cause of dysphagia was extraluminal mediastinal lymphadenopathy and in others direct tumour infiltration of the oesophagus. A tracheo-oesophageal fistula (TEF) was seen in 8 patients (19%). Most of the patients (32 patients; 76%) had stage 3 dysphagia (able to swallow liquids only) and the rest (10 patients; 24%) stage 4 (unable to swallow saliva). Thirty stents (71%) were partially covered and 12 (29%) were fully covered. Five (12%) stents have been placed across the oesophagogastric junction due to infiltration of the cardia. There were no immediate complications except for aspiration pneumonia in 3 (7%) and minor bleeding in 2 (5%) patients which resolved spontaneously. Dysphagia score improved in all patients to stage 1 (dysphagia with certain solid food in 16 patients-38%) or stage 2 (able to swallow semi solid in 26 patients-62%). In 3 (7%) patients during the follow-up we encountered tumour overgrowth and in 1 patients the TEF was not sealed so they have been referred for gastrostomy. No other long term complications were recorded. Most of the patients (30 patients- 71%) died during the follow-up, with mean survival of 4 months (range 2-9) after the stent placement. CONCLUSION: Placing SEMS in patients with lung cancer is safe and highly effective in relieving dysphagia with significant improvement in quality of life.

Radiofrequency ablation for gastric antral vascular ectasia and radiation proctitis.

Gastric antral vascular ectasia (GAVE) and chronic radiation proctitis (CRP) are well-known causes of repeated gastrointestinal bleeding and iron deficiency anemia. Argon plasma coagulation (APC) is the most common endoscopic therapy used, but some patients need multiple APC sessions. Radiofrequency ablation (RFA) is recently used in GAVE and CRP treatment with promising results. In this case series, we analyzed data for 15 patients with GAVE and 5 patients with CRP that had multiple prior APC treatment. They were treated with RFA HALO 90 catheter (HALO90 Ablation Catheter System; Covidien, GI Solutions, Sunnyvale, CA) in our tertiary referral center. A total of 20 patients received 32 RFA procedures (8 in the CRP group and 24 in the GAVE group). The median number of the procedures was 2 (range 1-4). The hemoglobin levels in the GAVE group were 83 g/L pre-RFA and 98 g/L post-RFA and in the CRP group, 86 g/L pre-RFA and 103 g/L post-RFA. A total of 16/20 patients (80%) were transfusion-free after the completion of RFA treatment. Technical success of the treatment was 95% (19/20 patients). RFA can be safely and successfully used in APC refractory GAVE and CRP patients.

Endoscopic ultrasound elastography strain histograms in the evaluation of patients with pancreatic masses.

AIM: To investigate the accuracy of the strain histogram endoscopic ultrasound (EUS)-based method for the diagnostic differentiation of patients with pancreatic masses. METHODS: In a prospective single center study, 149 patients were analyzed, 105 with pancreatic masses and 44 controls. Elastography images were recorded using commercially available ultrasound equipment in combination with EUS linear probes. Strain histograms (SHs) were calculated by machine integrated software in regions of interest and mean values of the strain histograms were expressed as Mode 1 (over the mass) and Mode 2 (over an adjacent part of pancreatic tissue, representing the reference area). The ratio between Mode 2 and Mode 1 was calculated later, representing a new variable, the strain histogram ratio. After the final diagnosis was established, two groups of patients were formed: a pancreatic cancer group with positive cytology achieved by fine needle aspiration puncture or histology after surgery (58 patients), and a mass-forming pancreatitis group with negative cytology and follow-up after 3 and 6 mo (47 patients). All statistical analyses were conducted in SPSS 14.0 (SPSS Inc., Chicago, IL, United States). RESULTS: Results were obtained with software for strain histograms with reversed hue scale (0 represents the hardest tissue structure and 255 the softest). Based on the receiver operating characteristics (ROC) curve coordinates, the cut-off point for Mode 1 was set at the value of 86. Values under the cut-off point indicated the presence of pancreatic malignancy. Mode 1 reached 100% sensitivity and 45% specificity with overall accuracy of 66% (95%CI: 61%-66%) in detection of pancreatic malignant tumors among the patients with pancreatic masses. The positive and negative predictive values were 54% and 100%, respectively. The cut-off for the new calculated variable, the SH ratio, was set at the value 1.153 based on the ROC curve coordinates. Values equal or above the cut-off value were indicative of pancreatic malignancy. The SH ratio reached 98% sensitivity, 50% specificity and an overall accuracy of 69% (95%CI: 63%-70%). The positive and negative predictive values were 92% and 100%, respectively. CONCLUSION: SH showed high sensitivity in pancreatic malignant tumor detection but disappointingly low specificity. Slight improvements in specificity and accuracy were achieved using the SH ratio.

Combined use of clips and nylon snare ("tulip-bundle") as a rescue endoscopic bleeding control in a mallory-weiss syndrome.

Mallory-Weiss syndrome (MWS) accounts for 6-14% of all cases of upper gastrointestinal bleeding. Prognosis of patients with MWS is generally good, with a benign course and rare recurrence of bleeding. However, no strict recommendations exist in regard to the mode of action after a failure of primary endoscopic hemostasis. We report a case of an 83-year-old male with MWS and rebleeding after the initial endoscopic treatment with epinephrine and clips. The final endoscopic control of bleeding was achieved by a combined application of clips and a nylon snare in a "tulip-bundle" fashion. The patient had an uneventful postprocedural clinical course and was discharged from the hospital five days later. To the best of our knowledge, this is the first case report showing the "tulip-bundle" technique as a rescue endoscopic bleeding control in the esophagus.