Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.

Improved nutritional outcomes and gastrointestinal symptoms in adult cystic fibrosis patients treated with elexacaftor/tezacaftor/ivacaftor.

INTRODUCTION: CFTR modulator therapy improves nutritional status and quality of life. Clinical trials have shown pancreatic insufficiency conversion, mostly in pediatric patients treated with ivacaftor. Studies with elexacaftor/tezacaftor/ivacaftor (ETI) in older patients have not suggested restoration of exocrine pancreas function, but quality data in adults are lacking. Our aim was to show the effect of ETI in adults with CF on nutritional status and digestive function. We hypothesized improvement of nutritional parameters and gastrointestinal symptoms, reduction of pancreatic enzyme replacement therapy, but uncertain improvement in exocrine pancreatic function. METHODS: We prospectively enrolled adults with CF treated with ETI from August 2021 to June 2022. We measured anthropometric parameters, laboratory nutritional markers, change of fecal elastase, pancreatic enzymes replacement therapy needs, and gastrointestinal symptoms. RESULTS: In the cohort of 29 patients (mean age 29.1 years), 82.8% suffered exocrine pancreatic insufficiency. After ETI, mean BMI increased by 1.20 kg/m2 (p < 0.001), mean body weight by 3.51 kg (p < 0.001), albumin by 2.81 g/L, and prealbumin by 0.06 (both p < 0.001). Only one patient, initially pancreatic insufficient (4.5%, p < 0.001), developed pancreatic sufficiency, indicated by increased fecal elastase from 45 µg/g to 442.1 µg/g. Mean change in lipase substitution decreased by 1,969 units/kg/day (p < 0.001) and stools frequency by 1.18 per day (p < 0.001). CONCLUSION: Our data suggest increased nutritional parameters, lower pancreatic substitution requirements, and improved defecation in adult CF patients on ETI. Improvement in exocrine pancreatic function might be mutation-specific and needs further study.

Unusual Biliary Complication following Christmas Eve Dinner.

We present a case of a fish bone impacted in the papilla of Vater resulting in dyspepsia and mild elevation in liver function tests, which was subsequently treated endoscopically. Fish bones are one of the most commonly encountered swallowed foreign bodies. However, involvement of the biliary tract, such as the one described by us, represents an extremely rare complication of fish bone ingestion. The diagnosis of a foreign body in the biliary tract can be difficult, and early endoscopic or surgical extraction may be required to avoid complications such as biliary stone formation, obstructive jaundice, cholangitis or cholecystitis, and/or biliary sepsis. Prompt endoscopic treatment can avoid severe biliary complications or surgical therapy.

Risk factors of pancreatic cancer and their possible uses in diagnostics.

Pancreatic cancer (PC) is a form of malignancy of increasing incidence and poor prognosis, with an average of less than 10% of patients surviving 5 years after being diagnosed. The main reason for this unfavorable situation is the long asymptomatic course of the disease, and the absence of a simple screening method, typically leading to the late discovery of the disease. The development of the malignancy from the initial carcinogenesis into invasive pancreatic carcinoma takes approximately 10 years. However, the progression of pancreatic cancer from early into advanced stages can be, according to the latest studies, incredibly fast, just a few months. Early stages of pancreatic malignancy can be detected only by expensive, and sometimes invasive, diagnostic methods (CT, MRI, or EUS). Due to the current absence of a reliable non-invasive screening method, it is necessary to define a group of patients who have the highest risk of PC development, five to ten times higher risk compared to the regular population at a minimum. Risk factors combine in their effect; therefore, relative risks of PC development need to be summarized to obtain a total relative risk for each person. The main and non-influenceable risk factor in the development of PC is the increasing age. The other non-influenceable risk factor of PC is a genetic predisposition - family incidence of the disease can be detected in 4-16% of patients. Some specific genes and mutations, which can play a role in PC development have already been identified (for example mutation of the PRSS-1 gene). Among the influenceable risk factors of PC is primarily smoking; obesity can play a part in PC development as well. A higher risk of PC is observed in patients with chronic pancreatitis. Nowadays, the relationship between PC and diabetes mellitus (DM) is hotly discussed. In the case of long-standing DM, the risk of pancreatic cancer is two times higher compared to the healthy population. However, new-onset DM can be the first sign of still asymptomatic PC. These patients, with paraneoplastic DM caused by pancreatic cancer cells, represent approximately 1% of recently diagnosed patients. However, this group of patients is still too large for screening. Because of that, it is necessary to find specific criteria to distinguish classic DM from the paraneoplastic form. The application of these criteria can help with the better stratification of risk in patients with new-onset diabetes and hence, it can help to discover PC in its early stages.

Gastrointestinal and hepatic symptoms of tickborne diseases.

While investigating patients with gastrointestinal (GI) and/or hepatic symptoms, tickborne diseases are only rarely considered to be the cause. However, the Czech Republic is an endemic region for several of tickborne diseases and, therefore, they should be a part of differential diagnosis of GI symptoms of unknown origin. This article describes GI and hepatic symptoms of several tickborne diseases - Lyme disease, ehrlichiosis, Rocky mountain spotted fever, tularemia, Colorado tick fever, tickborne relapsing fever, Q fever and babesiosis. GI and hepatic symptoms are quite common in Lyme disease patients. The prognosis is generally favourable with antibiotics treatment, however, serious courses have been described. Lyme disease should be a part of differential diagnosis of liver tests elevation and GI symptoms in patients from endemic regions regardless erythema migrans presence. Ehrlichiosis should be a part of differential diagnosis of acute febrile illness with GI symptoms especially in the presence of leukopenia/thrombocytopenia and/or liver tests elevation. Tularemia should be considered as a rare etiology of cholestatic hepatopathy and a history of a tick bite. In general, the importance of careful patient interviewing, including the history of a tick bite, can be highlighted also as a part of investigation of patients with seemingly unrelated GI and/or hepatic symptoms.

[Adherence to the guidelines for treatment of mild biliary acute pancreatitis in the setting of tertiary center in the Czech Republic]. / Casování chirurgické a endoskopické terapie akutní biliární pankreatitidy v podmínkách terciární nemocnice v Ceské republice.

INTRODUCTION: Cholecystectomy (CCX) represents the crucial procedure in preventing relapses of biliary acute pancreatitis (BAP). Endoscopic papilosphincterotomy (EPST) represent an acceptable alternative in patients unsuitable for surgery. Current guidelines recommend patients with mild BAP to undergo CCX in 2 maximally 4 weeks following discharge from the hospital, ideally during the same hospital stay. Adherence to the guidelines differs significantly between particular countries and institutions. AIM: To evaluate adherence to the guidelines of BAP management in conditions of tertiary hospital in the Czech Republic. METHODS: Retrospective analysis of consecutive patients hospitalized in the Clinic of Gastroenterology, University Hospital Brno for acute pancreatitis in years 2007-2012. Cases with both sonographic findings of lithiasis/sludge and 3-fold AST/ALT elevation were considered of clearly biliary etiology. RESULTS: We identified 328 patients treated for acute pancreatitis. Clearly biliary etiology was identified in 116 cases (54 male, 62 female). From 114 analyzed patients with complete documentation 81 underwent CCX, 23 were not operated and 10 cases were patients with history of previous CCX. Total mortality of the group was 5.3%. Out of 81 patients who had CCX was 48 cases of mild BAP. CCX was done during the same hospital stay and/or within 4 weeks from dismissal in 20 patients, therefore, current guidelines were followed in 41.7% of our study group. Eighteen out of the remaining 28 patients underwent ERCP with EPST. Therefore, within 4 weeks from dismissal 75% of our patients underwent a procedure (CCX and/or EPST) with a potential to reduce the risk of BAP recurrence. CONCLUSION: When longer (4 weeks) interval between mild BAP and CCX is applied, the current guidelines are followed in 41.7% of patients treated at our institution, which is comparable with the literature data. As much as 75% of our patients underwent a procedure (CCX and/or EPST) with a potential to reduce the risk of BAP recurrence. However, only 12.5% of index CCX is not favorable outcome that needs improvement. Similar difficulties are being dealt with in the most countries in the World.

Principles of Palliative and Supportive Care in Pancreatic Cancer: A Review.

Pancreatic adenocarcinoma (PDAC) is well known for its poor survival time. Clinical symptoms are painless jaundice or abdominal or back pain. Less specific symptoms often appear that make diagnosis difficult, e.g., weight loss, loss of appetite, nausea and vomiting, and general weakness. Only 10-20% of patients are diagnosed at an early stage. A cure is practically only possible with a radical surgical operation. In the case of locally advanced findings, neoadjuvant therapy is administered. Among the therapeutic options offered are chemotherapy, radiotherapy (including stereotactic radiotherapy-SBRT), targeted treatment, or immunotherapy. In the case of metastatic disease, of which more than half are present at diagnosis, the goal is to relieve the patient of problems. Metastatic PDAC can cause problems arising from the localization of distant metastases, but it also locally affects the organs it infiltrates. In our review article, we focus on the largest group of patients, those with locally advanced disease and metastatic disease-symptoms related to the infiltration or destruction of the pancreatic parenchyma and the growth of the tumor into the surrounding. Therefore, we deal with biliary or duodenal obstruction, gastric outlet syndrome, bleeding and thromboembolic diseases, pain, depression, and fatigue, as well as pancreatic exocrine insufficiency and malnutrition. Metastatic spread is most often to the liver, peritoneum, or lungs. The presented overview aims to offer current therapeutic options across disciplines. In accordance with modern oncology, a multidisciplinary approach with a procedure tailored to the specific patient remains the gold standard.

Management of pheochromocytomas and paragangliomas: Review of current diagnosis and treatment options.

Pheochromocytomas (PCCs) are rare neuroendocrine tumors derived from the chromaffin cells of the adrenal medulla. When these tumors have an extra-adrenal location, they are called paragangliomas (PGLs) and arise from sympathetic and parasympathetic ganglia, particularly of the para-aortic location. Up to 25% of PCCs/PGLs are associated with inherited genetic disorders. The majority of PCCs/PGLs exhibit indolent behavior. However, according to their affiliation to molecular clusters based on underlying genetic aberrations, their tumorigenesis, location, clinical symptomatology, and potential to metastasize are heterogenous. Thus, PCCs/PGLs are often associated with diagnostic difficulties. In recent years, extensive research revealed a broad genetic background and multiple signaling pathways leading to tumor development. Along with this, the diagnostic and therapeutic options were also expanded. In this review, we focus on the current knowledge and recent advancements in the diagnosis and treatment of PCCs/PGLs with respect to the underlying gene alterations while also discussing future perspectives in this field.

Update on the Role of Rifaximin in Digestive Diseases.

Various environmental factors affecting the human microbiota may lead to gut microbial imbalance and to the development of pathologies. Alterations of gut microbiota have been firmly implicated in digestive diseases such as hepatic encephalopathy, irritable bowel syndrome and diverticular disease. However, while these three conditions may all be related to dysfunction of the gut-liver-brain axis, the precise pathophysiology appears to differ somewhat for each. Herein, current knowledge on the pathophysiology of hepatic encephalopathy, irritable bowel syndrome, and diverticular disease are reviewed, with a special focus on the gut microbiota modulation associated with these disorders during therapy with rifaximin. In general, the evidence for the efficacy of rifaximin in hepatic encephalopathy appears to be well consolidated, although it is less supported for irritable bowel syndrome and diverticular disease. We reviewed current clinical practice for the management of these clinical conditions and underlined the desirability of more real-world studies to fully understand the potential of rifaximin in these clinical situations and obtain even more precise indications for the use of the drug.

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.

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).

Skin manifestations of pancreatic diseases.

Although symptoms of pancreatic diseases such as pancreatitis, acute and chronic and, carcinoma of the pancreas are mainly gastrointestinal in nature, the extra-pancreatic symptoms are also important. These include skin symptoms, such as pancreatic panniculitis, acanthosis nigricans, livedo reticularis, necrolytic migratory erythema, cutaneous signs of hemorrhage, as in persons with severe acute pancreatitis, or the finding of cutaneous metastases of pancreatic carcinoma, which may be a sign of advanced disease. The pancreas is therefore one of those organs for which diagnosis and therapy are often multidisciplinary. In this review article, we summarize current knowledge of the possible skin manifestations of pancreatic disorders.

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.

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.

The Role of Circulating MicroRNAs in Patients with Early-Stage Pancreatic Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is increasing in incidence and is still associated with a high rate of mortality. Only a minority of patients are diagnosed in the early stage. Radical surgery is the only potential curative procedure. However, radicality is reached in 20% of patients operated on. Despite the multidisciplinary approach in resectable tumors, early tumor recurrences are common. Options on how to select optimal candidates for resection remain limited. Nevertheless, accumulating evidence shows an important role of circulating non-coding plasma and serum microRNAs (miRNAs), which physiologically regulate the function of a target protein. miRNAs also play a crucial role in carcinogenesis. In PDAC patients, the expression levels of certain miRNAs vary and may modulate the function of oncogenes or tumor suppressor genes. As they can be detected in a patient's blood, they have the potential to become promising non-invasive diagnostic and prognostic biomarkers. Moreover, they may also serve as markers of chemoresistance. Thus, miRNAs could be useful for early and accurate diagnosis, prognostic stratification, and individual treatment planning. In this review, we summarize the latest findings on miRNAs in PDAC patients, focusing on their potential use in the early stage of the disease.

Autoimmune Diseases of Digestive Organs-A Multidisciplinary Challenge: A Focus on Hepatopancreatobiliary Manifestation.

It is well known that some pathological conditions, especially of autoimmune etiology, are associated with the HLA (human leukocyte antigen) phenotype. Among these diseases, we include celiac disease, inflammatory bowel disease, autoimmune enteropathy, autoimmune hepatitis, primary sclerosing cholangitis and primary biliary cholangitis. Immunoglobulin G4-related diseases (IgG4-related diseases) constitute a second group of autoimmune gastrointestinal, hepatobiliary and pancreatic illnesses. IgG4-related diseases are systemic and rare autoimmune illnesses. They often are connected with chronic inflammation and fibrotic reaction that can occur in any organ of the body. The most typical feature of these diseases is a mononuclear infiltrate with IgG4-positive plasma cells and self-sustaining inflammatory response. In this review, we focus especially upon the hepatopancreatobiliary system, autoimmune pancreatitis and IgG4-related sclerosing cholangitis. The cooperation of the gastroenterologist, radiologist, surgeon and histopathologist is crucial for establishing correct diagnoses and appropriate treatment, especially in IgG4 hepatopancreatobiliary diseases.

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.

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.

Increased markers of oxidative stress in plasma of patients with chronic pancreatitis.

OBJECTIVES: Chronic pancreatitis (CP) is a heterogeneous disease defined as chronic inflammatory changes of the pancreatic tissue caused by variety of aetiologies. Oxidative stress accompanying the inflammatory processes has been suggested as an important factor contributing to CP development. The aim of this study was to determine levels of lipid peroxidation products malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), together with nitrites and the total antioxidant capacity in the plasma of patients with CP and control subjects. DESIGN: One hundred and five patients with chronic pancreatitis and twenty seven healthy controls were included into this study. Levels of MDA and 4-HNE were analyzed using high-performance liquid chromatography. The total antioxidant capacity of plasma against peroxyl radicals was evaluated using chemiluminescent determination. Nitrites were determined using Griess reaction. Biochemical and haematological parameters were measured by standard methods. RESULTS: The plasma levels of both MDA and 4-HNE, together with the plasma levels of nitrites, were significantly higher in CP patients, compared to healthy controls. The total antioxidant capacity did not differ significantly. Biochemical parameters were in the normal range. The MDA and 4-HNE levels correlated positively with the levels of high-density lipoprotein cholesterol. Nitrite levels correlated positively with C-reactive protein, total white blood cells, and triglycerides. CONCLUSION: The significantly increased plasma levels of MDA, 4-HNE, and nitrites indicate that oxidative stress is present in patients with CP and that it may play a role in initiation and maintenance of inflammation within the pancreatic tissue in CP patients.

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.