Is autoimmune pancreatitis a risk factor for pancreatic adenocarcinoma?

Immunoglobulin G4-related diseases (IgG4-RD) are a group of diseases characterized by high serum levels of immunoglobulin G4 (IgG4), increased lymphocyte and plasma cell with IgG4 positivity in the parenchyma of some organs, and storiform fibrosis. The most frequently affected organ is the pancreas. This is an autoimmune form of pancreatitis, which can be divided into two types: Type 1, which is significantly more common than Type 2, is high in IgG4 in the pancreatic parenchyma and shows a fundamental difference in the noted presence of extrapancreatic disorders. In general, chronic inflammation is a risk factor in the development of carcinomas. Chronic pancreatitis is an accepted risk factor for the development of pancreatic cancer. The question is whether this also applies to autoimmune pancreatitis (AIP), which has some mediators of inflammation in common with sporadic pancreatitis, and what role the presence of IgG4 plays. The vast majority of the work on this topic consists of case reports, yet, even based on our own experience, we would like to say that there is a relationship between the autoimmune form of pancreatitis and pancreatic cancer, which usually occurs in the first two years after diagnosis of AIP. Also significant is the fact that the group of people with AIP, who is a clinical manifestation of IgG4-RD, was found to have an even higher incidence of extrapancreatic cancer than in the pancreas itself. Differentiating AIP from pancreatic cancer can sometimes be problematic since these diseases can both present as focal pancreatic lesions. IgG4 has been considered useful for AIP diagnosis, however, IgG4 levels can be slightly elevated, as in the case with pancreatic adenocarcinoma. IgG4 levels of over twice the upper limit are rare among patients with pancreatic adenocarcinoma. However, cases of simultaneous presentation of pancreatic cancer and AIP have been documented and should not be neglected. AIP is a condition where regular followup is mandatory, including from the perspective of possible cancerogenesis.

Nonalcoholic Fatty Pancreas Disease: Clinical Consequences.

Metabolic syndrome and its components such as obesity, hypertriglyceridemia, type-2 diabetes mellitus (DM-T2), and arterial hypertension are unequivocally serious problems for every society. This is especially true in economically developed countries where the imbalance in lifestyle between caloric intake and caloric output still gets greater and greater. This fact is not only a concern for the adult population but for children as well. However, metabolic syndrome does not only affect society and health in regards to cardiovascular diseases, it significantly concerns gastroenterology where it is classified as nonalcoholic fatty pancreas disease (NAFPD). The data gained from several trials show that the prevalence of NAFDP is 33% (95% CI 24-41%). When it comes to the diagnostic procedures concerning the presence of pancreatic fat, a whole spectrum of suitable methods are recommended. Probably, the most exact method is the use of magnetic resonance imaging. However, for common clinical practice, the abdominal sonographic examination based on the comparison of the pancreatic parenchymatous echogenity versus renal or hepatic echogenity is used. The clinical consequences of pancreatic steatosis and steatopancreatitis are significant. These diseases are connected with DM-T2 and insulin resistance. In recent years, changes of exocrine pancreatic function, particularly its decrease, have also been described. It is known that there is a close correlation between NAFPD and nonalcoholic hepatic steatosis and also with the increased thickness of aortic intima-media. There is also an important relationship between NAFPD and pancreatic carcinoma. Pancreatic steatosis, and especially its NAFPD form, is a serious state which can be treatable by the possible effective management of metabolic syndrome parameters, including obesity.

ERCP in patients after choledochodenoanastomosis.

The aim of this retrospective study is to evaluate our experience with diagnostic and therapeutic endoscopic retrograde cholangiopancreaticography (ERCP) in patients after choledochoduodenoanastomosis. METHODS: The study took 20 years (November 1994 - December 2014). Three patients after choledochoduodenoanastomosis who had symptoms of biliary obstruction were retrospectively evaluated. In all cases, a standard therapeutic videolateroscope was used to perform ERCP. PATIENTS AND RESULTS: We achieved ERCP in these 3 patients with choledochoduodenoanastomosis 100% cannulation success rate - 3 out of 3 patients. This was 100% success rate of diagnostic ERCP. In all of these patients, ERCP was found - both stenosis of the natural mouth of the Vater papilla, stenosis of choledochoduodenoanastomosis, and suprastenotic distal choledocholithiasis. In all patients with the above-described ERCP pathology, endoscopic treatment was initiated immediately after diagnostic ERCP, consisting of standard endoscopic papillotomy of the stenotic Vater papilla, balloon dilatation of choledochoduodenoanastomosis stenosis, and endoscopic extraction of suprastenotic distal choledocholithiasis. In total, therapeutic ERCP was completely successful in all 3 patients out of 3 (100%) who had initially started endoscopic treatment. There were no complications in our group of 3 patients. CONCLUSION: In ERCP in patients after choledochoduodenoanastomosis, we achieved 100% success of both diagnostic and therapeutic ERCP in all of our 3 patients.

Bone Metabolism in Inflammatory Bowel Diseases 2.

Inflammatory Bowel Disease encompasses Crohns Disease, which is capable of affecting the entire GI tract, although usually favors the ileocolonic and perianal areas, and Ulcerative Colitis, which is limited to the colon. The pathophysiology is not fully understood but is thought to be caused by a complex interplay among gut microbiota, dysregulation of the hosts immune system, genetic susceptibility and environmental factors. Osteopenia and osteoporosis are considered to be extraintestinal manifestations of inflammatory bowel disease. Osteoporosis is usually diagnosed by dual-energy X-ray absortiometry. Early interventions to treat active CD and preventative treatment strategies to reduce excessive bone loss might prevent long term consequences of bone loss, including fractures. The immune response in IBD includes increased production of variety of proinflammatory cytokines such as IL1β, TNFα, IL6 a IL1 from T cells and macrophages. These have both direct and indirect effects on bone turnover. Vitamin D is vital in mantenance of bone strenght, mineralisation and fracture prevention. Vitamin Ds physiological importance has also been implicated in a number of inflammatory diseases, mainly asthma, atherosclerosis and autoimmune disease.

Bone metabolism in inflammatory bowel diseases 1.

Inflammatory Bowel Disease encompasses Crohns Disease, which is capable of affecting the entire GI tract, although usually favors the ileocolonic and perianal areas, and Ulcerative Colitis, which is limited to the colon. The pathophysiology is not fully understood but is thought to be caused by a complex interplay among gut microbiota, dysregulation of the hosts immune system, genetic susceptibility and environmental factors. Osteopenia and osteoporosis are considered to be extraintestinal manifestations of inflammatory bowel disease. Osteoporosis is usually diagnosed by dual-energy X-ray absortiometry. Early interventions to treat active CD and preventative treatment strategies to reduce excessive bone loss might prevent long term consequences of bone loss, including fractures. The immune response in IBD includes increased production of variety of proinflammatory cytokines such as IL1β, TNFα, IL6 a IL1 from T cells and macrophages. These have both direct and indirect effects on bone turnover. Vitamin D is vital in mantenance of bone strenght, mineralisation and fracture prevention. Vitamin Ds physiological importance has also been implicated in a number of inflammatory diseases, mainly asthma, atherosclerosis and autoimmune disease.

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.

Endoscopic diagnostics and therapy of pancreatobiliary diseases in persons after gastric resection according to Billroth I.

The stomach resection according to Billroth I (B I) is very rarely done. The aim of this retrospective study is to evaluate our experience with diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in patients after stomach resection according to Billroth I. In patients with a condition after stomach resection according to B I, a study of the group of 20 years (November 1994 - December 2014) took place. Three patients were evaluated retrospectively after B I stomach resection with biliary obstruction. For the ERCP was used the Olympus therapeutic videotheroscop in all cases with the standard (as in normal anatomical situation). Cannulation success in diagnostic ERCP was achieved in 3 out of 3 patients - 100% success rate of ERC diagnosis. For all these 3 patients CDL was found in the ERCP. In addition, endoscopic treatment was performed immediately after ERCP diagnosis in all 3 patients with a CDL pathologic ERCP diagnosis, the initial endoscopic papillotomy (EPT) performed in the standard procedure (as in normal anatomy). Subsequently, endoscopic extraction of all CDL from hepatocholedocus to duodenum was performed. Overall the ERCP was completely successful in all 3 of the 3 (100% of 3) patients who initially started endoscopic therapy. There were no complications in our group of 3 patients. For ERCP in patients with BI stomach resection, we had 100% success rate of diagnostic and therapeutic ERCP in all of these patients (3 CDL patients).

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.

Fatty pancreas disease: clinical impact.

Pancreatic steatosis is the name for a state characterized by an increased accumulation of fat in the pancreas. It is most frequently due to obesity and the metabolic syndrome, other etiological factors may include some congenital syndromes, toxic substances or viral diseases. Diagnostics is based on non-invasive imaging methods. The most accessible is abdominal ultrasound, also endoscopic ultrasound, computed tomography or magnetic resonance imaging can be used. In clinical practice, pancreatic steatosis is in particular significant because of its close association with type 2 diabetes mellitus, non-alcoholic fatty liver disease and cardiovascular diseases. The disorder may aggravate the burden of acute pancreatitis, examined is its relationship to pancreatic cancer. Significant are also surgical reports on complications after pancreatic surgeries on individuals with pancreatic steatosis. Key words: acute pancreatitis - dyslipidemia - fatty pancreas - non-alcoholic fatty pancreas disease - non-alcoholic steatopancreatitis - obesity - pancreatic carcinoma.

[Adiponectin in patients with metabolic syndrome and diseases of the liver, bile ducts and pancreas]. / Adiponektin u nemocných s metabolickým syndromem a chorobami jater, zlucových cest a pankreatu.

Epidemiological data show that the metabolic syndrome can be diagnosed in up to 30 % of the population. Regarding 5 components of the metabolic syndrome, three of them, in case of positivity (visceral obesity, arterial hypertension, hypertriglyceridemia, changes of HDL-cholesterol levels and type 2 diabetes mellitus), are pathogenic factors which are the most frequently related to cardiovascular diseases, but currently they are also the focus of interest for gastroenterologists. The relationship between non-alcoholic hepatic steatosis, including non-alcoholic steatohepatitis, has been described. Less is known so far about the relation to the pancreas disease, particularly with respect to the status referred to as non-alcoholic fatty pancreas disease. The hormone selectively produced by adipose tissue is adiponectin. This protein is studied as a possible biomarker in people with metabolic syndrome, including obesity. Besides that, there is a question studied whether adiponectin can also play a significant role in the pathogenesis of diseases associated with fat building up in parenchymatous organs. Finding a reliable biomarker for patients with metabolic syndrome or diseases of the liver, biliary system and pancreas in relation to metabolic syndrome, presents a big challenge. And adiponectin is one of the promising biomarkers.Key words: adiponectin - biliary disease - metabolic syndrome - pancreatic steatosis - steatohepatitis.

[A contribution to the differential diagnostics of sclerosing cholangitides]. / Príspevek k diferenciální diagnostice sklerozujících cholangitid.

Sclerosing cholangitides represent a group of chronic biliary obstructive diseases which include primary sclerosing cholangitis (PSC), IgG4 associated sclerosing cholangitis (IgG4-SC) and secondary sclerosing cholangitis (SSC). The manifestations of the diseases are similar, but their asymptomatic course is also frequent. IgG4-SC belongs to the group of IgG4 associated diseases and it is the most frequently related to type 1 autoimmune pancreatitis. Diagnosing of IgG4-SC is based on typical histopathological images, shape changes revealed by diagnostic imaging, serological tests, concurrent impairment of other organs and response to therapy, where IgG4-SC responds well to treatment with corticoids, whereas the only possibility for the remaining units is endoscopic intervention or liver transplantation. Secondary sclerosing cholangitis may develop as a result of many different insults affecting the biliary tree. Among them, the most frequently described include long-lasting biliary obstruction, surgical injury of the biliary tree, and ischemic cholangitis in liver allotransplants or recurrent pancreatitis. We use serological and imaging examination in PSC diagnostics, sometimes we have to resort to liver biopsy. PSC is to a significant degree accompanied by the presence of idiopathic bowel disease, typically ulcerative colitis. As a result, PSC may lead to cirrhosis of the liver and it is a precancerous condition of several malignancies. With regard to variable locations of the biliary tree injuries concerning the aforementioned units, also certain malignancies in subhepatic landscape need to be considered in the differential diagnosis: pancreatic cancer and cholangiogenous carcinoma.Key words: genetic factors - IBD - IgG4 cholangitis - liver transplantation - bile duct cancer - ursodeoxycholic acid - primary sclerosing cholangitis - secondary cholangitis - sclerosing cholangitis.

Use of Magnetic Resonance Imaging to Quantify Fat and Steatosis in the Pancreas in Patients after Bariatric Surgery: a Retrospective Study.

INTRODUCTION: Pancreatic steatosis (PS) has both metabolic consequences and local effects on the pancreas itself. Magnetic resonance imaging (MRI) is the most reliable non-invasive method for diagnosing PS. We investigated the impact of metabolic syndrome (MS) on the presence of PS, differences in individuals with and without PS, and the metabolic effects of bariatric procedures. METHODS: Changes in anthropometric and basic biochemistry values and MS occurrence were evaluated in 34 patients with obesity who underwent a bariatric procedure. After the procedure, patients underwent MRI with manual 3D segmentation mask creation to determine the pancreatic fat content (PFC). We compared the differences in the PFC and the presence of PS in individuals with and without MS and compared patients with and without PS. RESULTS: We found no significant difference in the PFC between the groups with and without MS or in the occurrence of PS. There were significant differences in patients with and without PS, especially in body mass index (BMI), fat mass, visceral adipose tissue (VAT), select adipocytokines, and lipid spectrum with no difference in glycemia levels. Significant metabolic effects of bariatric procedures were observed. CONCLUSIONS: Bariatric procedures can be considered effective in the treatment of obesity, MS, and some of its components. Measuring PFC using MRI did not show any difference in relation to MS, but patients who lost weight to BMI < 30 did not suffer from PS and had lower overall fat mass and VAT. Glycemia levels did not have an impact on the presence of PS.

Helicobacter pylori infection and other bacteria in pancreatic cancer and autoimmune pancreatitis.

Helicobacter pylori (H. pylori) is an infectious agent influencing as much as 50% of the world's population. It is the causative agent for several diseases, most especially gastric and duodenal peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma of the stomach. A number of other, extragastric manifestations also are associated with H. pylori infection. These include neurological disorders, such as Alzheimer's disease, demyelinating multiple sclerosis and Parkinson's disease. There is also evidence for a relationship between H. pylori infection and such dermatological diseases as psoriasis and rosacea as well as a connection with infection and open-angle glaucoma. Generally little is known about the relationship between H. pylori infection and diseases of the pancreas. Most evidence about H. pylori and its potential role in the development of pancreatic diseases concerns pancreatic adenocarcinoma and autoimmune forms of chronic pancreatitis. There is data (albeit not fully consistent) indicating modestly increased pancreatic cancer risk in H. pylori-positive patients. The pathogenetic mechanism of this increase is not yet fully elucidated, but several theories have been proposed. Reduction of antral D-cells in H. pylori-positive patients causes a suppression of somatostatin secretion that, in turn, stimulates increased secretin secretion. That stimulates pancreatic growth and thus increases the risk of carcinogenesis. Alternatively, H. pylori, as a part of microbiome dysbiosis and the so-called oncobiome, is proven to be associated with pancreatic adenocarcinoma development via the promotion of cellular proliferation. The role of H. pylori in the inflammation characteristic of autoimmune pancreatitis seems to be explained by a mechanism of molecular mimicry among several proteins (mostly enzymes) of H. pylori and pancreatic tissue. Patients with autoimmune pancreatitis often show positivity for antibodies against H. pylori proteins. H. pylori, as a part of microbiome dysbiosis, also is viewed as a potential trigger of autoimmune inflammation of the pancreas. It is precisely these relationships (and associated equivocal conclusions) that constitute a center of attention among pancreatologists, immunologists and pathologists. In order to obtain clear and valid results, more studies on sufficiently large cohorts of patients are needed. The topic is itself sufficiently significant to draw the interest of clinicians and inspire further systematic research. Next-generation sequencing could play an important role in investigating the microbiome as a potential diagnostic and prognostic biomarker for pancreatic cancer.

Nutritional consequences of endoluminal gastroplasty in the treatment of morbidly obese patients.

BACKGROUND: The Endoscopic sleeve gastroplasty (ESG) is one of the new advanced restrictive techniques of bariatric endoscopy. The principle of this bariatric technique is the reduction of stomach volume through endoscopic plication. The long-term efficacy and metabolic effects of this procedure are the subject of this study. METHODS: 20 patients were enrolled; four men, sixteen women. Then they were followed for 24 months in terms of glycemic control, body composition, vitamin, and nutritional status. Observed parameters included glucose, triacylglycerols, high- and low-density lipoprotein cholesterol, micro and macro nutrients, fat mass, and lean body mass. RESULTS: We observed significant weight loss and a decrease body composition resulted from procedure vs. baseline, with levels of blood glucose also showing statistically significant reductions. The most notable decline in measured values was observed in period six months after the procedure. No significant changes were observed in measurement of micronutrients. CONCLUSIONS: Good restriction results were obtained following ESG, which might be mediated via altered glucose metabolism. The ESG method has shown a positive effect on fat and muscle mass. Unlike surgical methods, there were no deficits or deficiencies, especially in terms of essential vitamin levels.

Causes of Exocrine Pancreatic Insufficiency Other Than Chronic Pancreatitis.

Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malnutrition, results from primary pancreatic disease or is secondary to impaired exocrine pancreatic function. Although chronic pancreatitis is the most common cause of EPI, several additional causes exist. These include pancreatic tumors, pancreatic resection procedures, and cystic fibrosis. Other diseases and conditions, such as diabetes mellitus, celiac disease, inflammatory bowel disease, and advanced patient age, have also been shown to be associated with EPI, but the exact etiology of EPI has not been clearly elucidated in these cases. The causes of EPI can be divided into loss of pancreatic parenchyma, inhibition or inactivation of pancreatic secretion, and postcibal pancreatic asynchrony. Pancreatic enzyme replacement therapy (PERT) is indicated for the conditions described above presenting with clinically clear steatorrhea, weight loss, or symptoms related to maldigestion and malabsorption. This review summarizes the current literature concerning those etiologies of EPI less common than chronic pancreatitis, the pathophysiology of the mechanisms of EPI associated with each diagnosis, and treatment recommendations.

Autoimmune pancreatitis - An ongoing challenge.

Autoimmune pancreatitis is a rare form of chronic pancreatitis. The first descriptions of the disease date back to the 1990s. Etiology is multifactorial, with the use of genetic, environmental and complex immunological mechanisms. It is classified into two subtypes. Type 1 is part of a group of diseases called IgG4-related disease. Clinically is autoimmune pancreatitis manifested by icterus and abdominal discomfort. It can rarely present as acute pancreatitis. There is also a completely asymptomatic form of the disease. The diagnosis is based on abnormalities in histology, imaging methods, serology, the involvement of other organs in relation to IgG4-related disease, and a significant positive response to corticosteroid therapy. Differential diagnosis between the focal form of autoimmune pancreatitis and pancreatic cancer can be complicated, with endosonography playing an important role. In the treatment, we use corticosteroids and other immunosuppressants including biological therapy. Patients with the asymptomatic disease should also be treated to prevent late complications and exocrine and endocrine insufficiency. In addition to drug treatment, endoscopic and/or surgical treatment may be necessary. Even after recovery, the disease can relapse. The relationship between autoimmune pancreatitis and malignancies has not been clearly confirmed. The goal of this review is to provide a comprehensive look at autoimmune pancreatitis and translate latest scientific knowledge into clinical practice.