Grażyna Rydzewska

The results of severe acute pancreatitis treatment with continuous regional arterial infusion of protease inhibitor and antibiotic: a randomized controlled study.

Objectives: A randomized controlled trial was conducted to clarify whether continuous regional arterial infusion (CRAI) of protease inhibitor and antibiotic could reduce mortality rate of severe acute pancreatitis (SAP). Methods: Seventy-eight patients with SAP were included in the study. Thirty-nine patients were treated with CRAI, 31 patients completed the study; and another group of 39 patients was treated without CRAI therapy. Groups were well matched in clinical characteristics. The CRAI patients were treated continuously with nafamostat mesylate 240 mg/d and imipenem 1 g/d for 5 days via one of the arteries perfusing the pancreas. Later, imipenem was given intravenously (0.5 g every 8 hours) for 9 days. The non-CRAI patients received imipenem (0.5 g every 8 hours) intravenously for 14 days. Statistical analysis of the intention-to-treat (ITT) group was performed. Results: Lack of septic complications was observed in 23 patients with CRAI therapy and 20 non-CRAI patients (not significant). The additional antibiotics were applied in 8 of CRAI patients and in 18 non-CRAI (ITT, P = 0.02). Mortality rate was 5.1% in CRAI and 23.1% in non-CRAI group (ITT, P = 0.02). Urgent surgical intervention was necessary in 10.3% CRAI patients and in 33.3% non-CRAI (ITT, P = 0.01). Conclusions: The results show that CRAI of protease inhibitor and antibiotic is effective in preventing complications and in reducing mortality rate in SAP.

Clinical Effects of a Topically Applied Toll-like Receptor 9 Agonist in Active Moderate-to-Severe Ulcerative Colitis

Background and Aims: Toll-like receptors [TLRs] are potential drug targets for immunomodulation. We determined the safety and efficacy of the TLR-9 agonist DNA-based immunomodulatory sequence 0150 [DIMS0150] in ulcerative colitis [UC] patients refractory to standard therapy. Methods: In this randomized, double-blind, placebo-controlled trial, 131 patients with moderate-to-severe active UC were randomized to receive two single doses of the oligonucleotide DIMS0150 [30 mg] or placebo administered topically during lower GI endoscopy at baseline and Week 4. The primary endpoint was clinical remission, defined as Clinical Activity Index [CAI] ≤4, at Week 12. Secondary endpoints included mucosal healing and symptomatic remission of key patient-reported outcomes [absence of blood in stool and weekly stool frequency <35]. Results: There was no statistical significant difference between the groups in the induction of clinical remission at Week 12, with 44.4% in the DIMS0150 group vs. 46.5% in the placebo group. However, the proportion of patients who achieved symptomatic remission was 32.1% in the DIMS0150 group vs. 14.0% in the placebo group at Week 4 [p = 0.020], and 44.4% vs. 27.9% at Week 8 [p = 0.061]. More patients on DIMS0150 compared with those on placebo had mucosal healing [34.6% vs. 18.6%; p = 0.09] and histological improvement regarding the Geboes score [30.9% vs. 9.3%; p = 0.0073] at Week 4. Significantly more patients on DIMS0150 were in clinical remission with mucosal healing at Week 4: 21% vs. 4.7% in the placebo group [p = 0.02]. DIMS0150 was well tolerated, and no safety signals compared with placebo were evident. Conclusions: Therapy with the topically applied TLR-9 agonist DIMS0150 is a promising and well-tolerated novel therapeutic option for treatment-refractory, chronic active UC patients, warranting further clinical trials.

Neuroendocrine neoplasms of the small intestine and the appendix — management guidelines (recommended by the Polish Network of Neuroendocrine Tumours)

We present revised Polish guidelines regarding the management of patients harbouring neuroendocrine neoplasms (NENs) of the small intestine and appendix. The small intestine, especially the ileum, is the most common origin of these neoplasms. Most of them are well differentiated with slow growth. Rarely, they are less differentiated, growing fast with a poor prognosis. Since symptoms can be atypical, the diagnosis is often accidental. Typical symptoms of carcinoid syndrome occur in less than 10% of patients. The most useful laboratory marker is chromogranin A; 5-hydroxyindoleacetic acid is helpful in the monitoring of carcinoid syndrome. Ultrasound, computed tomography, magnetic resonance imaging, colonoscopy, video capsule endoscopy, balloon enteroscopy and somatostatin receptors scintigraphy are used in the visualisation. A histological report is crucial for the proper diagnostics and therapy of NENs, and it has been extensively described. The treatment of choice is surgery, either radical or palliative. Somatostatin analogues are crucial in the pharmacological treatment of the hormonally active and non-active small intestine NENs and NENs of the appendix. Radioisotope therapy is possible in patients with a good expression of somatostatin receptors. Chemotherapy is not effective in general. Everolimus therapy can be applied in patients with generalised NENs of the small intestine in progression and where there has been a failure or an inability to use other treatment options. Finally, we make recommendations regarding the monitoring of patients with NENs of the small intestine and appendix.

Tissue plasminogen activator, plasminogen activator inhibitor, and other parameters of fibrinolysis in the early stages of taurocholate acute pancreatitis in rats

SummaryIt is well known that fibrinolytic activity in the early stages of acute experimental pancreatitis (AEP) as assessed by euglobulin lysis time (ELT) is depressed. The aim of this study was to evaluate changes in the fibrinolytic system in the early stages of taurocholate AEP in rats. Tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor 1 (PAI-1) activity, plasminogen, α1 proteinase inhibitor (α1PI), α2 antiplasmin (α2AP), antithrombin III (AT III), fibrinogen, and ELT were measured 0.5, 1, 3, and 6 h after the induction of taurocholate AEP in rats, as well as in sham-operated animals and the control group, which was not submitted to any operation. T-PA activity decreased significantly after 3 and 6 h of AEP; PAI activity had a time course reverse to t-PA and was parallel to α1 PI activity. ELT was slightly prolonged after 0.5, 1, and 3 h, whereas α2 AP activity and plasminogen levels increased significantly; AT III activity was increased after 1 h in comparison to control group. Sham operation caused nonsignificant changes in fibrinolysis. Increase of PAI activity and decrease of t-PA could be a reasonable explanation for inhibited plasma euglobulin fibrinolytic activity noted in the early period of AEP.

Fluid resuscitation in acute pancreatitis: Normal saline or lactated Ringer's solution?

AIM To investigate whether administration of Ringers solution (RL) could have an impact on the outcome of acute pancreatitis (AP). METHODS We conducted a retrospective study on 103 patients [68 men and 35 women, mean age 51.2 years (range, 19-92 years)] hospitalized between 2011 and 2012. All patients admitted to the Department of Gastroenterology of the Central Clinical Hospital of the Ministry of Interior (Poland) with a diagnosis of AP who had disease onset within 48 h of presentation were included in this study. Based on the presence of persistent organ failure (longer than 48 h) as a criterion for the diagnosis of severe AP (SAP) and the presence of local complications [diagnosis of moderately severe AP (MSAP)], patients were classified into 3 groups: mild AP (MAP), MSAP and SAP. Data were compared between the groups in terms of severity (using the revised Atlanta criteria) and outcome. Patients were stratified into 2 groups based on the type of fluid resuscitation: the 1-RL group who underwent standard fluid resuscitation with a RL 1000 mL solution or the 2-NS group who underwent standard fluid resuscitation with 1000 mL normal saline (NS). All patients from both groups received an additional 5% glucose solution (1000-1500 mL) and a multi-electrolyte solution (500-1000 mL). RESULTS We observed 64 (62.1%) patients with MAP, 26 (25.24%) patients with MSAP and 13 (12.62%) patients with SAP. No significant difference in the distribution of AP severity between the two groups was found. In the 1-RL group, we identified 22 (55.5%) MAP, 10 (25.5%) MSAP and 8 (20.0%) SAP patients, compared with 42 (66.7%) MAP, 16 (24.4%) MSAP and 5 (7.9%) SAP cases in the 2-NS group (P = 0.187). The volumes of fluid administered during the initial 72-h period of hospitalization were similar among the patients from both the 1-RL and 2-NS groups (mean 3400 mL vs 3000 mL, respectively). No significant differences between the 1-RL and 2-NS groups were found in confirmed pancreatic necrosis [10 patients (25%) vs 12 patients (19%), respectively, P = 0.637]. There were no statistically significant differences between the 1-RL and 2-NS groups in the percentage of patients who required enteral nutrition (23 patients vs 17 patients, respectively, P = 0.534). Logistic regression analysis confirmed these findings (OR = 1.344, 95%CI: 0.595-3.035, P = 0.477). There were no significant differences between the 1-RL and 2-NS groups in mortality and the duration of hospital stay (median of 9 d for both groups, P = 0.776). CONCLUSION Our study failed to find any evidence that the administration of RL in the first days of AP leads to improved clinical outcomes.

Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours)

An increased interest in gastro-entero-pancreatic neuroendocrine neoplasms (GEP NENs) has recently been observed. These are rare neoplasms and their detection in recent years has improved. Over 50% of GEP NENs are carcinoids, and they are usually found incidentally during surgery in the small intestine and appendix and at diagnosis in distant metastases, mainly to the liver. There is a need for co-operation between specialists in various disciplines of medicine in order to work out the diagnostic and therapeutic guidelines. In this publication, we present general recommendations of the Polish Network of Neuroendocrine Tumours for the management of patients with GEP NENs, developed at the Consensus Conference which took place in Kamień Śląski in April 2013. Members of the guidelines working groups were assigned sections of the 2008 guidance to update. In the subsequent parts of this publication, we present the rules of diagnostic and therapeutic management of: - neuroendocrine neoplasms of the stomach and duodenum (including gastrinoma); - pancreatic neuroendocrine neoplasms; - neuroendocrine neoplasms of the small intestine and the appendix; - colorectal neuroendocrine neoplasms. The proposed recommendations by Polish and foreign experts representing different fields of medicine (endocrinology, gastroenterology, surgery, oncology, nuclear medicine and pathology) will be helpful in the diagnosis and treatment of GEP NENs patients.

Biosimilar medicines - their use in the treatment of inflammatory bowel diseases. Position statement of the Working Group of the Polish National Consultant in Gastroenterology.

Biological medical products are drugs whose active components are produced only by living, genetically modified organisms or live cell cultures. Patents and exclusivity for most biopharmaceuticals has either expired or will expire soon, which enables biotechnological companies to introduce similar biological products. The problem of replacing a biological medicine with a biosimilar in the course of therapy remains open. In this statement, the Working Group of the Polish National Consultant in Gastroenterology, in the absence of data regarding bioequivalence in patients with inflammatory bowel disease, does not recommend switching from original biological medicine to its biosimilar analogue in the course of treatment in inflammatory disease patients; however, this may change after receiving the results of controlled studies regarding bioequivalence in this group.

Pancreatic cyst fluid analysis for differential diagnosis between benign and malignant lesions

The majority of pancreatic cysts are detected incidentally when abdominal imaging is performed during unrelated procedures. The aim of the present study was to assess the diagnostic utility and clinical value of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9) and amylase analysis in pancreatic cyst fluid. The study included 52 patients with pancreatic cystic lesions, who underwent fine-needle aspiration biopsy to collect cystic fluid for cytological and biochemical analysis. Cysts were classified as benign (simple cysts, pseudocysts and serous cystadenomas) in 36 patients or premalignant/malignant (mucinous cyst-adenomas, intraductal papillary mucinous neoplasm and cystadenocarcinomas) in 16 patients. CEA and CA 19-9 were elevated in patients with malignant cysts (238±12.5 ng/ml and 222±31.5 U/ml, respectively) compared with benign lesions (34.5±3.7 ng/ml and 18.5±1.9 U/ml, respectively; P<0.001). Based on these results, the sensitivity and specificity of CEA were 91.8 and 63.9% and of CA 19-9 were 81.3 and 69.4%, respectively. Mean amylase levels in benign lesions (27825.7±91.9 U/l) were higher compared with malignant pancreatic cysts (8359.2±32.7 U/l; P<0.05). Cyst fluid analysis may prove a safe and useful adjunct for the differential diagnosis of pancreatic cystic lesions. In the present study, promising results for CEA and CA 19-9 have been demonstrated, however, the clinical value of these molecules must be confirmed.

Genetic architecture differences between pediatric and adult-onset inflammatory bowel diseases in the Polish population.

Most inflammatory bowel diseases (IBDs) are classic complex disorders represented by common alleles. Here we aimed to define the genetic architecture of pediatric and adult-onset IBDs for the Polish population. A total of 1495 patients were recruited, including 761 patients with Crohn’s disease (CD; 424 pediatric), 734 patients with ulcerative colitis (UC; 390 pediatric), and 934 healthy controls. Allelotyping employed a pooled-DNA genome-wide association study (GWAS) and was validated by individual genotyping. Whole exome sequencing (WES) was performed on 44 IBD patients diagnosed before 6 years of age, 45 patients diagnosed after 40 years of age, and 18 healthy controls. Altogether, out of 88 selected SNPs, 31 SNPs were replicated for association with IBD. A novel BRD2 (rs1049526) association reached significance of P = 5.2 × 10−11 and odds ratio (OR) = 2.43. Twenty SNPs were shared between pediatric and adult patients; 1 and 7 were unique to adult-onset and pediatric-onset IBD, respectively. WES identified numerous rare and potentially deleterious variants in IBD-associated or innate immunity-associated genes. Deleterious alleles in both groups were over-represented among rare variants in affected children. Our GWAS revealed differences in the polygenic architecture of pediatric- and adult-onset IBD. A significant accumulation of rare and deleterious variants in affected children suggests a contribution by yet unexplained genetic components.

Pancreatic neuroendocrine neoplasms — management guidelines (recommended by the Polish Network of Neuroendocrine Tumours)

We present revised diagnostic and therapeutic guidelines for the management of pancreatic neuroendocrine neoplasms (PNENs) proposed by the Polish Network of Neuroendocrine Tumours.These guidelines refer to biochemical (determination of specific and nonspecific neuroendocrine markers) and imaging diagnostics (EUS, CT, MR, and radioisotope examination with a 68Ga or 99Tc labelled somatostatin analogue).A histopathological diagnostic, which determines the further management of patients with PNENs, must be necessarily confirmed by immunohistochemical tests. PNENs therapy requires collaboration between a multidisciplinary team of specialists experienced in the management of these neoplasms. Surgery is the basic form of treatment. Medical therapy requires a multidirectional procedure, and therefore the rules of biotherapy, peptide receptor radionuclide therapy, chemotherapy and molecular targeted therapy are discussed.