Petr Dítě

The Role of Chronic Inflammation: Chronic Pancreatitis as a Risk Factor of Pancreatic Cancer

Pancreatic carcinoma is a condition with late diagnosis and one for which there is no effective screening method. One possible diagnostic approach of so-called early adenocarcinoma is the identification and systematic examination of individuals at risk for this condition. Between 1992 and 2005 we systematically observed 223 individuals diagnosed with chronic pancreatitis. In this 14-year period we performed classical biochemical tests, endoscopic ultrasound, CT scans and ERCP. We also asked about the number of cigarettes smoked per year and classified individuals consuming regularly more than 80 g of alcohol per day for 5 years for men and 50 g of alcohol per day for 5 years for women as having the alcoholic form of chronic pancreatitis. The remaining patients were classified according to the TIGARO classification. Alcohol-related etiology was detected in 73.1% of patients, 21.5% had the chronic obstructive form and only 5.4% were classified as idiopathic pancreatitis. Pancreatic carcinoma was detected in 13 patients with chronic pancreatitis (5.8%), 3 patients were diagnosed with gastric carcinoma and 1 with esophageal carcinoma. Pancreatic malignancy developed mainly in patients with the alcoholic form of pancreatitis (4.5%). In the 14-year period 11 subjects died, out of which 8 cases were related to pancreatic carcinoma. Pancreatic and extrapancreatic cancer localized in the gastrointestinal tract are serious complications of chronic nonhereditary pancreatitis. Systematic observation of patients with chronic pancreatitis must be performed with the aim of early diagnosis of pancreatic malignancies (but also including other types).

Intestinal Obstruction and Perforation – The Role of the Gastroenterologist

Intestinal obstruction belongs to highly severe conditions in gastroenterology, namely from the viewpoint of quick and correct diagnosis as well as at determining rational and effective therapy. Etiological multifactorial characteristics leading to processes resulting in mechanical or dynamic obstruction of the intestine, often referred to as paralytic ileus, are undoubtedly serious factors influencing the accuracy of diagnosis and therapeutic approach. Digestive endoscopy is a mandatory method in the diagnosis of intestinal obstructions. Diagnostic endoscopy, colonoscopy in the involvement of the large intestine or enteroscopy in the case of incomplete obstruction of the small intestine are the methods indicated in the majority of obstructive intestinal lesions. Besides their diagnostic importance, they also enable an effective therapeutic approach which may immediately follow the diagnostic intervention. Besides endoscopy that – due to the nature of performance – belongs to invasive methods, the diagnosis of obstructive intestinal processes is unthinkable without the use of non-invasive imaging methods. Abdominal ultrasound examination, a widely applied method, provides – under optimal examination conditions – information, e.g., about the width of the intestinal lumen or about the intestinal wall thickness; however, the specificity of investigation is not always sufficient. Both specificity and sensitivity of exploration are increased by a plain X-ray of the abdomen supplementing the ultrasound examination. Better results are achieved when the abdominal cavity is inspected by means of spiral CT examination that is nowadays not fashionably but highly effectively applied in the modification of the so-called CT enteroclysis or CT colonography. The usage of magnetic resonance (e.g. virtual colonography) is similar, but its efficacy is lower than that of CT examination. From a gastroenterologist’s perspective, endoscopic examination is the fundamental diagnostic and therapeutic method. However, endoscopic examination is initially limited by the cardiopulmonary state of the patient – in a number of cases, first the cardiopulmonary condition must be stabilized, dysbalance of water and mineral state must be restored, and only then can endoscopic investigation be carried out. The application of enteroscopy in small intestine disorders is only suitable in cases where air must be aspirated from the region of the stomach and mainly small intestine as it happens, for example, in acute intestinal pseudo-obstruction. The success of complex conservative therapy in these states is reached in 80% of the cases. In acute and complete intestinal obstruction, a surgical treatment performed in time is the only method. In these cases, the importance of identification of obstruction and timing of the intervention performance from the viewpoint of the patient’s survival is explicitly the principal and life-saving concern. In acute intestinal obstructions developing in patients with malignant affection of the intestine, it is necessary to choose – according to the obstruction location and general state of the patient – either urgently performed surgery or palliative endoscopic intervention which is the reduction of the intestinal lumen of the growing tumor mass and following insertion of a drain. This method also concerns lesions localized in the left half of the abdominal cavity, i.e. in the region of the rectosigmoid and descending part of the colon. Most patients in whom acute intestinal obstruction developed on the basis of malignant disease are risk and polymorbid subjects, and acute surgical intervention may be either impracticable or highly stressing. In such cases it is therefore helpful to insert a drain and to bridge the obstructed area after restoring the cardiopulmonary state including adjustment of the aqueous and mineral environment. Later, the performance of an elective surgical intervention is safer. Another alternative before inserting a drain is the dilatation of the stenotic site by means of a balloon, followed by stenting. Up until today, various types of intestinal drains have been introduced – they have always been self-expanding metallic stents. Just the application of self-expanding stents in patients with malignant intestinal obstruction and the endoscopic possibility of dilatations of benign intestinal obstructions with dilatation balloons are the most significant therapeutic contributions of digestive endoscopy in these states.

Immunoglobulin G4-Related Cholangitis: A Variant of IgG4-Related Systemic Disease

IgG4-related sclerosing cholangitis as part of IgG4 systemic-related diseases is commonly associated with autoimmune pancreatitis. Major clinical manifestations of IgG4-related sclerosing diseases are apparent in the organs in which tissue fibrosis with obstructive phlebitis is pathologically induced. IgG4-related sclerosing cholangitis is included within the heterogeneous group of ‘sclerosing cholangitis’. Sclerosing cholangitis may be associated with choledocholithiasis, infection or biliary malignancies. Sclerosing cholangitis of unknown etiology is called primary sclerosing cholangitis (PSC). Conservative therapy of PSC is usually unsuccessful, the disease involves extra- and/or intrahepatic biliary tree, and the end point of this disease is liver cirrhosis. Typically, PSC is identified at the age of 30 to 40 years, and the disease is frequently associated with inflammatory bowel diseases. On the other hand, IgG4-related sclerosing cholangitis is not associated with inflammatory bowel diseases. In patients with IgG4-related sclerosing cholangitis, a first symptom can be obstructive jaundice, whereas obstructive jaundice is rarely present in PSC. Clinically, patients with IgG4-related sclerosing cholangitis are older at diagnosis compared to patients with PSC. A typical diagnostic feature of IgG4-related sclerosing cholangitis is elevation of serum immunoglobulin G4. In patients with IgG4-related sclerosing cholangitis, response to steroid therapy is high; in patients with PSC corticosteroid therapy is unsuccessful. Histochemically abundant infiltration of IgG4-positive plasma cells is detected in the biliary duct wall. Histologically, we can identify dense lymphoplasmacytic infiltration of the bile duct wall, transmural fibrosis, lymphoplasmacytic infiltration and fibrosis in the periportal area of the liver – a typically obliterative phlebitis. The biliary epithelium is usually intact in contrast to PSC, where mucosal erosion is often present. Steroids are the first-choice therapy of IgG4-related sclerosing cholangitis. In the literature, cholangiocarcinoma in patients with IgG4- related sclerosing cholangitis was not described, whereas cholangiocarcinoma develops in up to 10–30% of patients with PSC.

Variceal bleeding in portal hypertension: bacterial infection and comparison of efficacy of intravenous and per-oral application of antibiotics--a randomized trial.

Objective To determine the prevalence of bacterial infection in patients admitted to hospital with variceal bleeding in comparison with patients with liver cirrhosis admitted because of another reason. To compare the effect of orally administered antibiotics vs. intravenous antibiotics. Methods Bacteriological investigation of blood culture, urine, throat smear, perianal smear and ascites (polymorphonuclear count as well in ascites) was made in 46 cirrhotic patients admitted to hospital with variceal bleeding and 48 cirrhotic patients admitted because of another reason. Bleeders were treated endoscopically (sclerotization) and pharmacologically (terlipressin 1 mg every 4 h for 5 days), and were randomly allocated to the treatment with oral norfloxacin (25 patients) or intravenous ampicillin/sulbactam (21 patients). Early and late mortalities were evaluated. Results The incidence of infection was high in both groups (63.0% bleeders vs. 54.2% controls), but bleeding patients more often had positive blood culture (17.3% vs. 8.6%) and statistically significantly more positive findings in the throat smears (36.9% vs. 17.3%, P=0.04), which gives the evidence of increased pathological colonization in these patients. No difference in survival was seen in patients with per-oral or intravenous administration of antibiotics. Conclusion Bacterial infection was demonstrated in high percentage in patients with liver cirrhosis admitted to hospital. The administration of antibiotics is indicated in these patients. Intravenous application is probably of the same efficacy as per-oral one.

Single balloon enteroscopy for endoscopic retrograde cholangiography in patients with Roux-en-Y hepaticojejuno anastomosis

AIM To evaluate single balloon enteroscopy in diagnostic and therapeutic endoscopic retrograde cholangiography (ERC) in patients with Roux-en-Y hepaticojejunoanastomosis (HJA). METHODS The study took place from January 2009 to December 2011 and we retrospectively assessed 15 patients with Roux-en-Y HJA who had signs of biliary obstruction. In total, 23 ERC procedures were performed in these patients and a single balloon videoenteroscope (Olympus SIF Q 180) was used in all of the cases. A transparent overtube was drawn over the videoenteroscope and it freely moved on the working part of the enteroscope. Its distal end was equipped with a silicone balloon that was inflated by air from an external pump at a pressure of ≤ 5.4 kPa. The technical limitations or rather the parameters of the single balloon enteroscope (working length - 200 cm, diameter of the working channel - 2.8 mm, absence of Albarran bridge) showed the need for special endoscopic instrumentation. RESULTS Cannulation success was reached in diagnostic ERC in 12 of 15 patients. ERC findings were normal in 1 of 12 patients. ERC in the remaining 11 patients showed some pathological changes. One of these (cystic bile duct dilation) was subsequently resolved surgically. Endoscopic treatment was initialized in the remaining 10 patients (5 with HJA stenosis, 2 with choledocholithiasis, and 3 with both). This treatment was successful in 9 of 10 patients. The endoscopic therapeutic procedures included: balloon dilatation of HJA stenosis - 11 times (7 patients); choledocholitiasis extraction - five times (5 patients); biliary plastic stent placement - six times (4 patients); and removal of biliary stents placed by us - six times (4 patients). The mean time of performing a single ERC was 72 min. The longest procedure took 110 min and the shortest took 34 min. This shows that it is necessary to allow for more time in individual procedures. Furthermore, these procedures require the presence of an anesthesiologist. We did not observe any complications in these 15 patients. CONCLUSION This method is more demanding than standard endoscopic retrograde cholangiopancreatography due to altered postsurgical anatomy. However, it is effective, safe, and widens the possibilities of resolving biliary pathology.

Unusual Multiorgan Immunoglobulin G4 (IgG4) Inflammation: Autoimmune Pancreatitis, Mikulicz Syndrome, and IgG4 Mastitis

Autoimmune pancreatitis (AIP) type 1 is commonly associated with simultaneous involvement of extrapancreatic organs. Sclerosing cholangitis, sialadenitis, retroperitoneal fibrosis, Sjögren syndrome, and other extrapancreatic lesions are often observed concurrently with AIP. High levels of immunoglobulin G4 (IgG4) in the blood serum and affected tissues are typical of this diagnostic entity. We describe a case report of a 58-year-old female with findings of AIP (according to Asian criteria), IgG4-positive mastitis, and histologically verified Mikulicz syndrome. The effect of corticoid therapy supported the diagnosis of AIP and simultaneously led to the eradication of recurrent mastitis. To the best of our knowledge, this is the first reported case of concurrent findings of AIP and IgG4 mastitis. Our case report supports the concept of systemic IgG4 syndrome with multisystem involvement. Timely diagnosis and appropriate therapy can be effective in a high percentage of patients.

New European initiatives in colorectal cancer screening: Budapest declaration

Colorectal cancer (CRC) is the second most common newly diagnosed cancer and the second most common cause of death in the European Union (EU). CRC is an enormous health and economic burden. Early detection and prevention have the possibility of reducing this burden significantly. Many cancer-associated deaths can be avoided through early detection by high-quality colorectal screening programs followed by appropriate treatment. Under the auspices of the United European Gastroenterology Federation (UEGF), the European Association for Gastroenterology and Endoscopy, the Hungarian Society of Gastroenterology and the Hungarian College of Gastroenterology, the ‘Budapest Declaration’ (2011) was an accepted official scientific program during the Hungarian Presidency of the Council of the European Union. The Budapest Declaration follows the Munich Declaration (2001), the Brussels Declaration (2007), the Transatlantic Declaration (2009), the Barcelona Declaration (2010), the written declaration of CRC screening, a joint initiative with European Parliamentarians coordinated by the UEGF, and finally, the ‘European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis’. The ‘Budapest Declaration’ together with previous declarations aims to urge the national and supranational healthcare decision makers to launch new Europe-wide initiatives to establish high-quality CRC programs to achieve optimal efficiency in CRC screening. In case of implementation of the proposals, actions and conditions recommended, we can achieve that one of the basic principles of the EU – the chance of equal access – be realized in member states with respect to the prevention of CRC and reduction of cancer-related mortality. To better achieve this goal, we propose to establish an UEGF joint committee, with one participant representing each EU member state to coordinate and supervise the implementation of CRC screening.

New European Initiatives in Colorectal Cancer Screening: Budapest Declaration. Official Appeal during the Hungarian Presidency of the Council of the European Union under the Auspices of the United European Gastroenterology Federation, the European Association for Gastroenterology and Endoscopy and the Hungarian Society of Gastroenterology

Colorectal cancer (CRC) is the second most common newly diagnosed cancer and the second most common cause of death in the European Union (EU). CRC is an enormous health and economic burden. Early detection and prevention have the possibility of reducing this burden significantly. Many cancer-associated deaths can be avoided through early detection by high-quality colorectal screening programs followed by appropriate treatment. Under the auspices of the United European Gastroenterology Federation (UEGF), the European Association for Gastroenterology and Endoscopy, the Hungarian Society of Gastroenterology and the Hungarian College of Gastroenterology, the ‘Budapest Declaration’ (2011) was an accepted official scientific program during the Hungarian Presidency of the Council of the European Union. The Budapest Declaration follows the Munich Declaration (2001), the Brussels Declaration (2007), the Transatlantic Declaration (2009), the Barcelona Declaration (2010), the written declaration of CRC screening, a joint initiative with European Parliamentarians coordinated by the UEGF, and finally, the ‘European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis’. The ‘Budapest Declaration’ together with previous declarations aims to urge the national and supranational healthcare decision makers to launch new Europe-wide initiatives to establish high-quality CRC programs to achieve optimal efficiency in CRC screening. In case of implementation of the proposals, actions and conditions recommended, we can achieve that one of the basic principles of the EU – the chance of equal access – be realized in member states with respect to the prevention of CRC and reduction of cancer-related mortality. To better achieve this goal, we propose to establish an UEGF joint committee, with one participant representing each EU member state to coordinate and supervise the implementation of CRC screening.

Autoimmune pancreatitis--recent advances.

Autoimmune pancreatitis (AIP) is recognized as a distinct clinical entity, identified as a chronic inflammatory process of the pancreas in which the autoimmune mechanism is involved. Clinically and histologically, AIP has two subsets: type 1 – lymphoplasmatic sclerosing pancreatitis with abundant infiltration of the pancreas and other affected organs with immunoglobulin G4-positive plasma cells, and type 2 – duct centric fibrosis, characterized by granulocyte epithelial lesions in the pancreas without systemic involvement. In the diagnosis of AIP, two diagnostic criterions are used – the HISORt criteria and Asian Diagnostic Criteria. In the differential diagnosis, the pancreatic cancer must be excluded by endosonographically guided pancreatic biopsy. Typical signs of AIP are concomitant disorders in other organs (kidney, liver, biliary tract, salivary glands, colon, retroperitoneum, prostate). Novel clinicopathological entity was proposed as an ‘IgG4-related sclerosing disease’ (IgG4-RSC). Extensive IgG4-positive plasma cells and T lymphocyte infiltration is a common characteristics of this disease. Recently, IgG4-RSC syndrome was extended to a new entity, characterized by IgG4 hypergammaglobulinemia and IgG4-positive plasma cell infiltration, this being considered an expression of a lymphoproliferative disease, ‘IgG4-positive multiorgan lymphoproliferative syndrome’. This syndrome includes Mikulicz’s disease, mediastinal fibrosis, autoimmune hypophysitis, and inflammatory pseudotumor – lung, liver, breast. In the therapy of AIP, steroids constitute first-choice treatment. High response to the corticosteroid therapy is an important diagnostic criterion. In the literature, there are no case-control studies that determine if AIP predisposes to pancreatic cancer. Undoubtedly, AIP is currently a hot topic in pancreatology.

Immunoglobulin G4, autoimmune pancreatitis and pancreatic cancer.

Background: Immunoglobulin G4 (IgG4)-related diseases are a group of diseases characterized by enlargement of the affected organs, elevation of serum IgG4, massive infiltration of affected organs with lymphocytes and plasma cells with IgG4 positivity and tissue fibrosis. Type I autoimmune pancreatitis is one form of IgG4-related disease. For IgG4-related diseases, various localizations are described for up to 10% of malignancies. The aim of our study was to examine IgG4 serum levels and pancreatic tissue with respect to the simultaneous presence of autoimmune pancreatitis in patients with pancreatic cancer. Methods: IgG4 serum levels were examined In 106 patients with histologically confirmed pancreatic cancer. The level of 135 mg/dl was considered as the normal value. Pancreatic tissue was histologically examined with respect to the presence of markers of autoimmune pancreatitis. Results: A higher IgG4 level than the cut-off value of 135 mg/dl was proven in 11 patients with pancreatic cancer. Of these 11 patients, 7 had levels twice the normal limit (65.6%). Autoimmune pancreatitis was diagnosed in these individuals. In the case of 1 patient, it was basically an unexpected finding; another patient was initially diagnosed with autoimmune pancreatitis. Repeated biopsy of the pancreas at the time of diagnosis did not confirm the presence of tumour structures, therefore steroid therapy was started. At a check-up 6 months after starting steroid therapy, the condition of the patient improved subjectively and IgG4 levels decreased. However, endosonographically, malignancy was suspected, which was subsequently confirmed histologically. This patient also demonstrated an IgG4 level twice the normal limit. Conclusion: IgG4-related diseases can be accompanied by the simultaneous occurrence of malignancies, which also applies to autoimmune pancreatitis. Chronic pancreatitis is considered a risk factor for pancreatic cancer. It cannot be reliably confirmed whether this also applies to autoimmune pancreatitis. In accordance with other works, however, it is evident that, despite the described high sensitivity and specificity for IgG4 elevation in the case of autoimmune pancreatitis, even levels twice the normal limit are demonstrable in some individuals with pancreatic cancer, without the presence of autoimmune pancreatitis. We believe that patients with IgG4-related disease, including autoimmune pancreatitis, must be systematically monitored with respect to the potential presence of malignancy.