The role of metabolic syndrome in the induction of chronic pancreatitis after a first attack of acute pancreatitis - multicenter trial.

BACKGROUND: Metabolic syndrome is a serious societal problem worldwide. In the Czech Republic more than 30% of the adult population are sufferers. The role of recurrent acute pancreatitis in the induction of chronic pancreatitis, following the socalled „mechanistic definition“ of chronic pancreatitis, has been unequivocally confirmed. However, there are a number of factors that may contribute to the development of chronic pancreatitis. The first aim of the study was to determine whether the metabolic syndrome may affect the development of chronic pancreatitis. The second question we asked ourselves was whether even one acute attack of pancreatitis could be an inductive factor in chronic pancreatitis. METHODS: Based on data obtained retrospectively from a total of 264 people diagnosed with chronic pancreatitis in 4 centers, a total of 59 people (22.3%) diagnosed within 36 months of a first attack of acute pancreatitis was obtained. Etiologies of either genetically induced pancreatitis or autoimmune pancreatitis were excluded. Diagnostics to identify the presence of metabolic syndrome were run on the 59 persons so obtained using the criteria from the socalled „harmonized“ definition of 2009 (obesity, arterial hypertension, hypertriglyceridemia, type 2 diabetes mellitus and a decreased level of HDL cholesterol). RESULTS: Comparing the findings of the individual components of metabolic syndrome in persons with chronic pancreatitis after a 1st attack of acute pancreatitis with the metabolic syndrome and in persons with chronic pancreatitis after the 1st attack of acute pancreatitis but without metabolic syndrome, a statistically significant difference in obesity was found (82.5% vs. 28.5%), hypertriglyceridemia (82.3% vs 17.8%) and arterial hypertension (70.5% vs 21.4%). The interval during which chronic pancreatitis occurred after acute pancreatitis averaged 12 months (10-14 months) in subjects with metabolic syndrome, whereas in the group without metabolic syndrome the interval was longer, 20 months (16-29 months). CONCLUSION: Our results show that even one attack of acute pancreatitis (regardless of etiology) can be an inductive factor in chronic pancreatitis. The presence of metabolic syndrome can accelerate the development of chronic pancreatitis after one has had acute pancreatitis.

Pancreatic Solid Focal Lesions: Differential Diagnosis between Autoimmune Pancreatitis and Pancreatic Cancer.

BACKGROUND: Diagnosis of pancreatic cancer (PC) in early stages is still challenging for gastroenterologists. The early detection of cancer is one of the utmost importance for the successful therapy of this malignancy. An accurate differential diagnosis of focal pancreatic lesions plays also an important role, whether it is differential diagnosis of chronic pancreatitis from PC or autoimmune pancreatitis (AIP) from PC. Raised serum immunoglobulin G4 (IgG4) levels to twice the normal value are considered one of significant diagnostic features of type 1 AIP. However, IgG4 can be increased also in patients with PC, but levels usually do not exceed twice the normal value. METHODS: In years 2012-2017, IgG4 serum levels were examined in 115 patients with histologically confirmed PC. Patients with PC and elevated IgG4 level (above 135 mg/dL) had tested their histological resection specimens or bioptic specimens from pancreatic lesion, with targeted detection of the presence of IgG4 and plasmocytes in the pancreatic tissue and changes characteristic for type 1 AIP. RESULTS: A plasmatic IgG4 level in 115 patients with diagnosed PC was higher than 135 mg/dL in 14 patients (12.2%). Out of them, 2 patients (1.7%) revealed a serum IgG4 level higher than double the normal value, that is, higher than 270.0 mg/dL (suggestive of AIP). One patient met histological criteria for diagnosis of AIP in the simultaneous presence of PC. CONCLUSION: Diagnosis of early cancer stages, particularly differentiating AIP from PC can be sometimes problematic. IgG4 levels can be slightly elevated also in case of PC. A targeted biopsy of the pancreas is the method of choice in cases suspected from a focal form of AIP and we recommend to prefer it over other modalities, such as, for example, response to steroid therapy.

Idiopathic inflammatory bowel disease and the first type of autoimmune form of pancreatitis: case report.

The autoimmune form of pancreatitis (AIP) is divided into the following two subtypes. The 1st subtype is characterized by the high presence of immunoglobulin G4 in the blood serum and tissue of some organs which are in the close connection to the so called IgG4 associated disorders. The typical diagnostic signs of AIP are the histomorphological changes. This type of AIP is more frequent than the 2nd type with which has however some common histomorphological signs and mainly the positive response to the administered steroids used in the initial treatment. Whilst the 1st type of AIP is typically connected to the disorders of various organs such are the biliary tract, salivary and lacrimal glands, retroperitoneal fibrosis, reins, prostate gland and the next ones, the 2nd type of AIP is significantly connected to the inflammatory bowel disease only. Inflammatory bowel diseases are rarely present in the 1st type of AIP on the contrary. In our case report we mention the first published observations performed in the Czech Republic when the 1st type of AIP is succeeded by the inflammatory bowel disease - Crohn´s disease.

[Relapsing autoimmune pancreatitis type 1: case report]. / Relabující autoimunitní pankreatitida 1. typu: kazuistika.

Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis, classified into 2 subtypes - AIP type 1 and AIP type 2. We present a case of a 31-years-old female admitted to our institution with upper abdominal pain and obstructive jaundice. Endoscopic retrograde cholangiopancreatoscopy (ERCP) revealed stenosis of intrapancreatic distal bile duct. Diffuse parenchymal enlargement and typical features of AIP were shown by computed tomography (CT) and endoscopic ultrasonography (EUS). The patient´s serum IgG4 was elevated at 3.8 g/l (range 0.08-1.4 g/l). She was diagnosed with AIP type 1 and treated with prednisone (initial dose of 30 mg per day, then tapered by 5 mg/day every week). The maintenance dose of 5 mg per day was continued for 6 months. Despite clinical and radiological remission, serum levels of IgG4 remained elevated. The patient experienced disease relapse 25 months after first attack. Moreover, new finding of calcifications occured in pancreas. The relapse was managed with corticosteroids and maintenance immunosupression with azathioprin was started. Literature review on risk factor of relapse, long-term immunosupressive therapy indication and optimal follow-up of AIP type 1 patients are discussed.Key words: autoimmune pancreatitis type 1 - long-term follow-up - relapse - therapy.

Surgical Treatment of Ampullary Adenocarcinoma - Single Center Experience and a Review of Literature.

BACKGROUND: Adenocarcinomas of ampulla of the Vater are relatively uncommon tumors of the gastrointestinal tract. In premalignant lesions endoscopic treatment predominate. According to some authors even early adenocarcinomas (limited to mucosa) can be solved endoscopically. In malignant lesions affecting deeper layers (including submucosa) surgical therapy is the most important. The article summarises the current view for a surgical treatment of ampullary adenocarcinomas and presents results concerning our group of patients. MATERIALS AND METHODS: In 2012-2016 a total number of 17 patients underwent resection for a tumor of ampulla of the Vater. Patients underwent standard staging, were presented before a multidisciplinary committee and referred to a surgical treatment. The main measured parameters were the type of surgical procedure, 30-day morbidity and mortality, histopathologic result and subsequent oncologic treatment. The Leeds Pathology Protocol was used to evaluate the specimens after pancreaticoduodenectomy (PD). RESULTS: PD (n = 9) was a more often performed procedure than the transduodenal surgical ampullectomy (TSA) (n = 8). TSA predominated in polymorbid patients. Histological results (n = 17) established adenoma with high-grade dysplasia in 4 patients, the diagnosis of adenocarcinoma was set in 13 patients. Eight patients underwent adjuvant oncologic therapy (2 had adjuvant chemotherapy, 6 had combination of chemoradiotherapy). CONCLUSION: Premalignant neoplasias of ampulla of the Vater can be mostly solved by endoscopy. If endoscopic resection is not possible surgical therapy is indicated. PD is preferred procedure in the diagnosis of adenocarcinoma. In high-risk and polymorbid patients, with no suspicion for a metastatic lymph nodes, TSA can be considered. Endoscopic ultrasonography is the imaging modality of choice for local staging of ampulla of the Vater and has important role in deciding between endoscopic, local surgical excision (TSA) or radical resection (PD). Our results confirmed rightfulness to perform TSA especially in elderly or polymorbid patients, where in histopathologic specimens evaluation in TSA procedures early T stage and more favorable grading predominated.Key words: adenocarcinoma of the ampulla of Vater - duodenum - endoscopic resection - ampullectomy - pancreaticoduodenectomy - surgery.

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.

[Autoimmune pancreatitis - diagnostic consensus]. / Autoimunitní pankreatitida - diagnostický konsenzus.

The autoimmune type of pancreatitis represents the specific disease of pancreas, with significant contribution of autoimmune processes in its etiopathogenesis. Currently, there are two proved subtypes of this particular pancreatopathy, which are defined clinically, histomorphologically and serologically. They have many histomorphological signs in common, but differ in the presence of so-called granulocytic epithelial lesions (GEL), which are absent in subtype 1. The subtype 1 is characterized by the presence of gammaglobulines, esp. immunoglobuline G4 and IgG4 positive extrapancreatic lesions. The subtype 2 is typically associated with the inflammatory bowel diseases, esp. ulcerative colitis. But the common characteristic of both subtypes is the fact response to applied steroid treatment. Due to diverse diagnostic criteria in the past, in 2011 the consensus for the diagnosis of autoimmune pancreatitis was announced. It is based on clinical symptoms, biochemical results, the results got by using of imaging methods, histomorphology and positive response to steroid treatment. The matter to be solved is the question of early differential diagnosis between focal autoimmune pancreatitis and adenocarcinoma of pancreatic head. From imaging methods are MRI/CT, MRCP (in Asia ERCP), EUS with targeted biopsy of the gland (under EUS control), are recommended as the methods of choice.

Endoscopic drainage treatment of pancreatic pseudocysts.

BACKGROUND/AIMS: This study presents the experience of its authors with endoscopic drainage treatment of pancreatic pseudocysts. The first part of the study offers a literature overview of the basic knowledge of pancreatic pseudocysts. The authors gradually deal with the individual types of pancreatic pseudocysts, the clinical picture, complications and diagnostics. Within the bounds of differential diagnostics the authors stress mainly the necessity of differentiating pancreatic pseudocysts from cystic tumors and benign cysts. Special attention is dedicated to various modalities of pancreatic pseudocyst treatment. The second part of the study presents the authors' own results of the endoscopic drainage treatment of pancreatic pseudocysts. METHODOLOGY: Results of endoscopic drainage treatment of pancreatic pseudocysts, which is one of significant possibilities of treatment of these conditions, are presented. RESULTS: This method was used to treat 33 patients (24 men and 9 women) from September 2007 to March 2009. Endoscopic drainage of pancreatic pseudocysts was performed 4 times transduodenally a 29 times transgastrically, namely in 6 cases under endosonographic guidance and in 27 cases by a duodenoscope after endosonographic targeting. CONCLUSIONS: The authors conclude that endoscopic drainage is an effective method of pancreatic pseudocyst treatment.

Pancreatic pain.

Pain is a common symptom of many diseases. Recently, the pain has been classified and analyzed exactly. Its particular components/types are described to the maximum of their depths and details. That is why each particular pain present in a specific disease (pancreatopathies included) has to be treated according to the presence of the specific type of pain. In diseases of pancreas, there are nociceptive, neuropathic, and inflammatory components of pain participating, frequently. Especially long-lasting, not well-controlled pain sets off the process of neuromodulation. The recent pioneering applications/administrations of various neuromodulatory therapeutic approaches represent the promising discoveries for the treatment of long-term, severe, drug-resistant pain syndromes, including chronic pancreatitis. In this article, we summarized the characteristics of pain, the therapeutic strategy, and algorithms of analgesic treatment (in general and applied for pancreatopathies), including new therapeutic trends and approaches.

Endoscopic drainage treatment of pancreatic pseudocysts.

BACKGROUND/AIMS: This study presents the experience of its authors with endoscopic drainage treatment of pancreatic pseudocysts. The first part of the study offers a literature overview of the basic knowledge of pancreatic pseudocysts. The authors gradually deal with the individual types of pancreatic pseudocysts, the clinical picture, complications and diagnostics. Within the bounds of differential diagnostics the authors stress mainly the necessity of differentiating pancreatic pseudocysts from cystic tumors and benign cysts. Special attention is dedicated to various modalities of pancreatic pseudocyst treatment. The second part of the study presents the authors' own results of the endoscopic drainage treatment of pancreatic pseudocysts. METHODOLOGY: Results of endoscopic drainage treatment of pancreatic pseudocysts, which is one of significant possibilities of treatment of these conditions, are presented. RESULTS: This method was used to treat 33 patients (24 men and 9 women) from September 2007 to March 2009. Endoscopic drainage of pancreatic pseudocysts was performed four times transduodenally and 29 times transgastrically, of which 6 cases were under endosonographic guidance and 27 cases by a duodenoscopy after endosonographic targeting. CONCLUSIONS: The authors conclude that endoscopic drainage is an effective method of pancreatic pseudocyst treatment.

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).

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.

Stereotactic Body Radiotherapy (SBRT) of Pancreatic Cancer-A Critical Review and Practical Consideration.

Pancreatic cancer is the third leading cause of cancer death in the developed world and is predicted to become the second by 2030. A cure may be achieved only with surgical resection of an early diagnosed disease. Surgery for more advanced disease is challenging and can be contraindicated for many reasons. Neoadjuvant therapy may improve the probability of achieving R0 resection. It consists of systemic treatment followed by radiation therapy applied concurrently or sequentially with cytostatics. A novel approach to irradiation, stereotactic body radiotherapy (SBRT), has the potential to improve treatment results. SBRT can deliver higher doses of radiation to the tumor in only a few treatment fractions. It has attracted significant interest for pancreatic cancer patients, as it is completed quickly, requires less time away from full-dose chemotherapy, and is well-tolerated than conventional radiotherapy. In this review, we aim to provide the reader with a basic overview of current evidence for SBRT indications in the treatment of pancreatic tumors. In the second part of the review, we focus on practical information with respect to SBRT treatment plan preparation the performance of such therapy. Finally, we discuss future directions related to the use of magnetic resonance linear accelerators.

Lipidomic profiling of human serum enables detection of pancreatic cancer.

Pancreatic cancer has the worst prognosis among all cancers. Cancer screening of body fluids may improve the survival time prognosis of patients, who are often diagnosed too late at an incurable stage. Several studies report the dysregulation of lipid metabolism in tumor cells, suggesting that changes in the blood lipidome may accompany tumor growth. Here we show that the comprehensive mass spectrometric determination of a wide range of serum lipids reveals statistically significant differences between pancreatic cancer patients and healthy controls, as visualized by multivariate data analysis. Three phases of biomarker discovery research (discovery, qualification, and verification) are applied for 830 samples in total, which shows the dysregulation of some very long chain sphingomyelins, ceramides, and (lyso)phosphatidylcholines. The sensitivity and specificity to diagnose pancreatic cancer are over 90%, which outperforms CA 19-9, especially at an early stage, and is comparable to established diagnostic imaging methods. Furthermore, selected lipid species indicate a potential as prognostic biomarkers.

PET/CT-tailored treatment of locally advanced oesophago-gastric junction adenocarcinoma: a report on the feasibility of the multicenter GastroPET study.

BACKGROUND: Perioperative chemotherapy is a recommended treatment approach for localised oesophago-gastric junction adenocarcinoma, but not all patients respond to neoadjuvant chemotherapy. Early identification of non-responders and treatment adaptation in the preoperative period could improve outcomes. GastroPET is a national, multicentre phase II trial evaluating a 18FDG-PET/CT-guided preoperative treatment strategy with the R0 resection rate as a primary endpoint. Here, we report on the accuracy of the methodology, the feasibility of the study design and patient safety data after enrolment of the first 63 patients. METHODS: Patients with locally advanced oesophago-gastric junction adenocarcinoma (Siewert I - III) stage Ib-IIIc underwent baseline 18FDG-PET/CT scanning and re-evaluation after 14 days of oxaliplatinum-5FU-(docetaxel) chemotherapy. Responders were defined by a ⩾ 35% decrease in tumour FDG standardised uptake value (SUV)average from baseline. Responders continued with the same chemotherapy for 2 to 3 months prior to surgery. PET-non-responders switched to preoperative chemoradiotherapy [weekly carboplatin and paclitaxel with concurrent radiotherapy (45 Gy in 25 fractions)]. Here, we aim to confirm the feasibility of FDG-PET-based response assessment in a multicenter setting and to compare local versus central reading. In addition, we report on the feasibility of the study conduct and patient safety data. RESULTS: A total of 64 patients received baseline and sequential 14-day 18FDG-PET/CT scanning. And, 63 were allocated to the respective treatment arm according to PET-response [35 (56%) responders and 28 (44%) non-responders]. The concordance of local versus central reading of SUV changes was 100%. Until the date of this analysis, 47 patients (28 responders and 19 non-responders) completed surgery. Postoperative complications of grade ⩾ 3 (Common Terminology Criteria for Adverse Events, CTCAE Version 5.0) were reported in five responders (18%; 95% CI: 7.9-36%) and two non-responders (11%; 95% CI: 2.9-31%), with no statistical difference (p = 0.685). One patient in each arm died after surgery, leading to a postoperative in-hospital mortality rate of 4.3% (2/47 patients; 95% CI: 1.2-14%). CONCLUSION: Local and central FDG-SUV quantification and PET-response assessment showed high concordance. This confirms the accuracy of a PET-response-guided treatment algorithm for locally advanced oesophago-gastric junction cancer in a multicenter setting. Preoperative treatment adaptation revealed feasible and safe for patients.

Incidence of pancreatic carcinoma in patients with chronic pancreatitis.

BACKGROUND/AIMS: Pancreatic carcinoma belongs to the area of conditions with late diagnosis and there is no effective screening method. One possible approach to diagnosing so called early adenocarcinoma, therefore, lies in the identification and systematic examination of individuals in risk for this condition. METHODOLOGY: 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 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 TIGARO classification. RESULTS: 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%), three patients were diagnosed with gastric carcinoma and one 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 eight cases were related to pancreatic carcinoma. CONCLUSION: Pancreatic and extra-pancreatic cancer localized in the gastrointestinal tract are among the serious complications of chronic nonhereditary pancreatitis. Systematic observation of patients with chronic pancreatitis must be performed with the aim of early diagnosis of pancreatic, but not only pancreatic malignancies.

GAPPS - Gastric Adenocarcinoma and Proximal Polyposis of the Stomach Syndrome in 8 Families Tested at Masaryk Memorial Cancer Institute - Prevention and Prophylactic Gastrectomies.

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare variant of familial adenomatous polyposis. It is an autosomal-dominant cancer-predisposition syndrome with massive polyposis of the stomach and a significant risk of gastric adenocarcinoma. Li et al., 2016, described point mutations in the Ying Yang 1 binding site of the APC gene 1B promoter associated with GAPPS syndrome. The first GAPPS syndrome in a Czech family was described in 2016. At Masaryk Memorial Cancer Institute, GAPPS syndrome was diagnosed in eight families using Sanger sequencing. In all families, one mutation in promoter 1B of APC gene NM_001127511: c.-191T>C was detected. This mutation was not found in any patient with multiple colon polyposis without a detected classic mutation in the APC gene. In total, 24 carriers of this mutation in promoter 1B of the APC gene were detected. Out of those 24 carriers, 20 had massive gastric polyposis with more than 100 fundic glandular polyps diagnosed between the age of 22 and 65, 5 had already died of adenocarcinoma of the stomach (at the ages of 29, 40, 59, 60 and 64, respectively) and another woman was treated at the age of 29. Two female carriers do not yet have polyposis of the stomach at the ages of 31 and 65, respectively; one female carrier has incipient polyposis at the age of 58. A male carrier does not have any clinical symptoms, gastroscopy was not indicated because of his age. Prophylactic total gastrectomy with D2 lymphadenectomy has already been performed 6 times at Masaryk Memorial Cancer Institute, in 5 cases without adenocarcinoma at the ages of 27, 34, 44, 51 and 66, respectively; in one female carrier adenocarcinoma of the stomach was detected in a histology specimen. Two prophylactic gastrectomies with D1 lymphadenectomy were performed at University Hospital Brno at the ages of 42 and 50, respectively. In the Czech Republic point mutation c.-191T>C (rs879253783) in the 1B promoter of the APC gene is a frequent cause of gastric polyposis with a high risk of gastric adenocarcinoma, even at a young age. Positively tested individuals are recommended to high-risk oncology clinic. A necessary part of the discussion with the patient is information about a preventive gastrectomy.

Autoimmune pancreatitis.

Autoimmune pancreatitis is a form of chronic pancreatitis of presumed autoimmune aetiology. The disease is characterised with clinical, serological, histomorphological and imaging features. Autoimmune pancreatitis is recognised as a T-cell-mediated specific disease with lymphoplasmatic infiltration of pancreatic tissue and pancreatic parenchyma fibrosis. Serum immunoglobulin IgG or IgG4 and antibodies (rheumatoid factor, lactoferrin antibodies, carbonic anhydrase II, etc) are usually increased. But the lack of specific biochemical markers is a major drawback in the diagnosis of autoimmune pancreatitis. The Japan Pancreas Society proposed diagnostic criteria for autoimmune pancreatitis as the presence antibodies, pancreas enlargement and pancreatic duct narrowing, lymphoplasmatic infiltration, response to corticosteroid therapy, and association with other autoimmune diseases such as autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, sialoadenitis, inflammatory bowel disease and Sjögren syndrome. New criteria (HISORt Criteria) incorporate imaging changes, organ involvement, specific elevation of IgG4 subclass and histopathological markers. Autoimmune pancreatitis could be associated with diabetes mellitus and exocrine pancreatic dysfunction. Clinically, autoimmune pancreatitis is a disease with mild symptoms; severe attacks of abdominal pain are not typical. Typically, pancreatic calcifications and pseudocyst are absent; on the other hand jaundice and/or pancreatic mass are frequent signs, and both make differential diagnosis with pancreatic cancer difficult. From a practical point of view, in an elderly male presenting with obstructive jaundice and pancreatic mass, autoimmune pancreatitis is one of the differential diagnoses to avoid unnecessary surgical therapy.

Tumor marker M2-pyruvate-kinase in differential diagnosis of chronic pancreatitis and pancreatic cancer.

BACKGROUND/AIMS: This study addresses the possibility of very difficult differential diagnosis of pancreatic cancer and chronic pancreatitis, especially in cases where pancreatic cancer appears in the course of chronic pancreatitis. A combination of graphical methods and pancreatic biopsy targeted with endosonography seems to be the most precise diagnostic technique. Even negative findings for this procedure cannot exclude the risk of existing tumor and is additionally an invasive technique. Therefore there are different conditions that have to be fulfilled to allow use of both endoscopic and bioptic instruments (biopsy with biopsy needle). Tumor markers of blood serum are used in the practice, but this use seems to be limited by the sensitivity, which is on the level of 60-70% in average. METHODOLOGY: The authors examined M2-pyruvate-kinase concentration in their group, which included patients with chronic pancreatitis, different grading of pancreatic cancer as well as patients with pancreatic cancer which appeared in the course of chronic pancreatitis. M2-pyruvate-kinase was used as a marker of tumor hyperplasia as it is present in higher concentration in tumors of gastrointestinal tract. RESULTS: The authors observed important growth in advanced forms of pancreatic tumor compared to patients with chronic pancreatitis. M2-PK was increased in a similar way in patients with pancreatic cancer in the course of chronic pancreatitis. The results led to the conclusion that evaluation of M2-PK concentration helps differentiating between pancreatic cancer and chronic pancreatitis, especially in cases where morphological changes of the gland have focal character and are imitating pancreatic cancer.