Background Pancreatic heterotopia (PH) is defined as ectopic pancreatic tissue outside the normal pancreas and its vasculature and duct system. Most frequently, PH is detected incidentally by histopathological examination. The aim of the present study was to analyze a large single-center series of duodenal PH with respect to the clinical presentation. Methods A prospective pancreatic database was retrospectively analyzed for cases of PH of the duodenum. All pancreatic and duodenal resections performed between January 2000 and October 2015 were included and screened for histopathologically proven duodenal PH. PH was classified according to Heinrich’s classification (Type I acini, ducts, and islet cells; Type II acini and ducts; Type III only ducts). Results A total of 1274 pancreatic and duodenal resections were performed within the study period, and 67 cases of PH (5.3%) were identified. The respective patients were predominantly male (72%) and either underwent pancreatoduodenectomy (n = 60); a limited pancreas resection with partial duodenal resection (n = 4); distal pancreatectomy with partial duodenal resection (n = 1); total pancreatectomy (n = 1); or enucleation (n = 1). Whereas 65 patients (83.5%) were asymptomatic, 11 patients (18.4%) presented with symptoms related to PH (most frequently with abdominal pain [72%] and duodenal obstruction [55%]). Of those, seven patients (63.6%) had chronic pancreatitis in the heterotopic pancreas. The risk of malignant transformation into adenocarcinoma was 2.9%. Conclusions PH is found in approximately 5% of pancreatic or duodenal resections and is generally asymptomatic. Chronic pancreatitis is not uncommon in heterotopic pancreatic tissue, and even there is a risk of malignant transformation. PH should be considered for the differential diagnosis of duodenal lesions and surgery should be considered, especially in symptomatic cases.

Background: Chronic pancreatitis (CP) often leads to recurrent pain as well as exocrine and/or endocrine pancreatic insufficiency. This study aimed to investigate the effect of pancreatic head resections on glucose metabolism in patients with CP. Methods: Patients who underwent pylorus-preserving pancreaticoduodenectomy (PPPD), Whipple procedure (cPD), or duodenum-preserving pancreatic head resection (DPPHR) for CP between January 2011 and December 2020 were retrospectively analyzed with regard to markers of pancreatic endocrine function including steady-state beta cell function (%B), insulin resistance (IR), and insulin sensitivity (%S) according to the updated Homeostasis Model Assessment (HOMA2). Results: Out of 141 pancreatic resections for CP, 43 cases including 31 PPPD, 2 cPD and 10 DPPHR, met the inclusion criteria. Preoperatively, six patients (14%) were normoglycemic (NG), 10 patients (23.2%) had impaired glucose tolerance (IGT) and 27 patients (62.8%) had diabetes mellitus (DM). In each subgroup, no significant changes were observed for HOMA2-%B (NG: p = 0.57; IGT: p = 0.38; DM: p = 0.1), HOMA2-IR (NG: p = 0.41; IGT: p = 0.61; DM: p = 0.18) or HOMA2-%S (NG: p = 0.44; IGT: p = 0.52; DM: p = 0.51) 3 and 12 months after surgery, respectively. Conclusion: Pancreatic head resections for CP, including DPPHR and pancreatoduodenectomies, do not significantly affect glucose metabolism within a follow-up period of 12 months.

Die Ätiologie von entzündlichen Pankreaserkrankungen, insbesondere bei den idiopathischen Pankreatitiden, ist weitgehend noch nicht verstanden. In der folgenden Arbeit sollen immunologische und molekularbiologische Aspekte zu Pankreaserkrankungen unter Berücksichtigung eigener Untersuchungen dargestellt werden. Zu Beginn unserer Arbeit haben wir untersucht inwieweit immunologische Veränderungen an der Entstehung einer chronischen Pankreatitis beteiligt sind. Wir fanden eine systemische Aktivierung des zellulären Immunsystems, ohne dass sich Unterschiede zwischen idiopathischer und alkoholtoxischer Pankreatitis ergaben. Im folgenden haben wir uns mit dem molekularbiologischen Hintergrund von entzündlichen und malignen Pankreaserkrankungen beschäftigt. Eine genetische Modellerkrankung ist die hereditäre Pankreatitis, deren genetische Ursache 1996 mit der Entdeckung zweier Mutationen im kationischen Trypsinogen entschlüsselt wurde. Mit der Identifizierung einer neuen Mutation im kationischen Trypsinogen und deren funktionellen Charakterisierung konnten wir hier zum weiteren Verständnis dieser Erkrankung beitragen. Weitere Untersuchungen beschäftigten sich mit dem genetischen Hintergrund bei Patienten mit idiopathischer Pankreatitis. Bei etwa 30% dieser Patienten fanden wir ein abnormales Allel im Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gen und bei einzelnen Patienten einen Polymorphismus im Serine Proteasen Inhibitor (SPINK1) Gen. Das zunehmende Wissen um genetische Veränderungen und deren Folgen setzt auch eine kritische Auseinandersetzung mit ethischen und rechtlichen Fragen voraus. Daher wurden während einer internationalen Konsensus Konferenz Richtlinien zum Umgang mit diesen Fragen erarbeitet. Die Assoziation von UGT1A7*3 Polymorphismus, welches ein Phase II Protein mit niedriger katalytischer Entgiftungsaktivität im Xenobiotika Stoffwechsel kodiert, mit dem Auftreten von Pankreaserkrankungen war Gegenstand weiterer Untersuchungen. Hierzu untersuchten wir Patienten mit alkoholischer chronischer Pankreatitis, Patienten mit einer SPINK1 Mutation und gesunde Kontrollen. Darüberhinaus betrachteten wir ein Kollektiv von Patienten mit einem Pankreaskarzinom. Unsere Ergebnisse belegen einen synergistischen negativen Effekt von exogenen Risikofaktoren (Alkohol, Nikotin) und genetischer Prädisposition. Die Rolle des oxidativen Stresses in der Genese von Pankreaserkrankungen wird damit untermauert. Erste therapeutische Ansätze aus den gewonnenen Erkenntnisses haben wir in einer prospektiven Studie mit einer immunmodulierenden und antioxidativ wirksamen Glutaminsubstitution bei Patienten mit akuter Pankreatitis gezeigt. Die Glutaminsubstitution führte zu einem besseren Krankheitsverlauf. / The etiology of inflammatory and malignat pancreatic disease are poorly understood. This thesis will discuss our results of immunological and genetic investigations in patients with inflammatory and malignat pancreatic diseases. Especially the background of idiopathic pancreatitis will be discussed. We started our investigations with immunological investigations and demonstrated an evidence for a systemic activated cellular immune system in patients with chronic pancreatitis irrespectively of the aetiology of pancreatitis. Further studies deal with the genetic background of pancreatitis. The discovery of the association between a mutation of the cationic trypsinogen gene and the hereditary pancreatitis was a milestone in the modern pancreatology. We contribute to the understanding of this disease by detecting a new mutation (D22G). We were able to functional characterise this mutation. Mutation of the activation peptides (D22G, K23R) are related to an increased release of trypsin in hydrolisation studies in vitro. In addition, our further investigations confirmed and extended the knowledge of the role of mutation in the CFTR gene and the SPINK 1 gene in patients with 'idiopathic' pancreatitis. Cognisant of the ethical and clinical responsibilities guidelines for the genetic testing and managing of patients with genetic diseases of the pancreas were developed. The low detoxification activity UGT1A7*3 polymorphism has been identified as a novel risk factor of pancreatic inflammatory and malignant diseases defining the interaction of genetic predisposition and environmentally induced oxidative injury. Based on this data we conducted a prospective, randomised clinical trial on the supplementation with glutamine in patients with acute pancreatitis shedulded for total parenteral nutrition. The administration of glutamine, which has been shown to have an immune-modulating and antioxidative capacity, was associated with a favourable clinical course of the patiens receiving glutamine.

<p>Акутни панкреатитис је ензиматско инфламаторно оболење панкреаса, са инциденцијом око 17/100000 становника. Најчешћи етиолошки чиниоци који се везују за ово стање су билијарна калкулоза (45%) и конзумација алкохолних пића (35%). Ређи узроци су одређени лекови, хипертриглицеридемија, хиперкалијемија, траума, урођени чиниоци, и идиопатски панкреатитис (20%). По међународној Атланској (Atlanta) класификацији, акутни панкреатитис се може манифестовати у умереној, умерено тешкој и тешкој форми. Умерене форме панкреатитиса се јављају у 80%, карактеришу се едемом органа и имају благ и краткотрајан клинички ток, са стопом морталитета од 1%. Основни циљ лечења болесника са акутним панкреатитисом у прва 24 сата хоспитализације јесте олакшавање тегоба, утврђивање узрока панкреатитиса и процена тежине обољења. Акутни панкреатитис билијарне етиологије узрокован је калкулозом жучне кесе и/ или жучних путева. Препоручени третман билијарне калкулозе, у циљу превенције поновног атака умерене форме билијарног панкреатитиса , подразумева уклањање жучне кесе лапароскопском холецистектомијом са интраоперативном холангиографијом. Уколико се дијагностикује калкулоза жучних канала ради се ендоскопска ретроградна холангиопанкреатографија (ЕРЦП) са ендоскопском папилотомијом (ЕПТ) и уклањем__ калкулуса и детритуса уз жучних водова, са циљем обезбеђивања нормалног протока жучи у дванаестопалачно црево. Циљ овог истраживања је оптимализација редоследа примене ЛХ и ЕРЦП са ЕПТ, идентификацијом предикционих показатеља холедохолитијазе, ради скраћења дужине хоспитализације болесника са умереном формом акутног билијарног панкреатитиса. У спроведеној проспективној анамнестичкој студији, учествовало је 100 болесника лечених од умерене форме акутног билијарног панкреатитиса, у Ургентном центру Клиничког центра Војводине, од 2011. до 2015.године, од којих је код 80 урађена само ЛХ, а код 20 ЛХ и ЕРЦП са ЕПТ. Анализом клиничких, ултразвучних и лабораторијских налаза, идентификовано је 5 статистички значајних предиктора холедохолитијазе; директни и укупни билирубин, алкална фосфатаза (АФ), гама глутирил транспепдидаза (гама ГТ) и це реактивни протеин (ЦРП), на основу којих је омогућено креирање математичког модела за предикцију холедохолитијазе, коришћењем теорије потпорних вектора (СВМ). Установљено је да патолошки налази ових параметара значајно указују на холедохолитијазу, те да је ЛХ препоручена као метода првог избора, код болесника код којих налази предиктора холедохолитијазе нису патолошки. Овако лечени болесници су имали значајно краће време хоспитализације. Поред тога, уколико се интраоперативном холангиографијом (ИОХ) при ЛХ установи холедохолитијаза, ЕРЦП са ЕПТ се може урадити без одлагања.</p> / <p>Akutni pankreatitis je enzimatsko inflamatorno obolenje pankreasa, sa incidencijom oko 17/100000 stanovnika. Najčešći etiološki činioci koji se vezuju za ovo stanje su bilijarna kalkuloza (45%) i konzumacija alkoholnih pića (35%). Ređi uzroci su određeni lekovi, hipertrigliceridemija, hiperkalijemija, trauma, urođeni činioci, i idiopatski pankreatitis (20%). Po međunarodnoj Atlanskoj (Atlanta) klasifikaciji, akutni pankreatitis se može manifestovati u umerenoj, umereno teškoj i teškoj formi. Umerene forme pankreatitisa se javljaju u 80%, karakterišu se edemom organa i imaju blag i kratkotrajan klinički tok, sa stopom mortaliteta od 1%. Osnovni cilj lečenja bolesnika sa akutnim pankreatitisom u prva 24 sata hospitalizacije jeste olakšavanje tegoba, utvrđivanje uzroka pankreatitisa i procena težine oboljenja. Akutni pankreatitis bilijarne etiologije uzrokovan je kalkulozom žučne kese i/ ili žučnih puteva. Preporučeni tretman bilijarne kalkuloze, u cilju prevencije ponovnog ataka umerene forme bilijarnog pankreatitisa , podrazumeva uklanjanje žučne kese laparoskopskom holecistektomijom sa intraoperativnom holangiografijom. Ukoliko se dijagnostikuje kalkuloza žučnih kanala radi se endoskopska retrogradna holangiopankreatografija (ERCP) sa endoskopskom papilotomijom (EPT) i uklanjem__ kalkulusa i detritusa uz žučnih vodova, sa ciljem obezbeđivanja normalnog protoka žuči u dvanaestopalačno crevo. Cilj ovog istraživanja je optimalizacija redosleda primene LH i ERCP sa EPT, identifikacijom predikcionih pokazatelja holedoholitijaze, radi skraćenja dužine hospitalizacije bolesnika sa umerenom formom akutnog bilijarnog pankreatitisa. U sprovedenoj prospektivnoj anamnestičkoj studiji, učestvovalo je 100 bolesnika lečenih od umerene forme akutnog bilijarnog pankreatitisa, u Urgentnom centru Kliničkog centra Vojvodine, od 2011. do 2015.godine, od kojih je kod 80 urađena samo LH, a kod 20 LH i ERCP sa EPT. Analizom kliničkih, ultrazvučnih i laboratorijskih nalaza, identifikovano je 5 statistički značajnih prediktora holedoholitijaze; direktni i ukupni bilirubin, alkalna fosfataza (AF), gama glutiril transpepdidaza (gama GT) i ce reaktivni protein (CRP), na osnovu kojih je omogućeno kreiranje matematičkog modela za predikciju holedoholitijaze, korišćenjem teorije potpornih vektora (SVM). Ustanovljeno je da patološki nalazi ovih parametara značajno ukazuju na holedoholitijazu, te da je LH preporučena kao metoda prvog izbora, kod bolesnika kod kojih nalazi prediktora holedoholitijaze nisu patološki. Ovako lečeni bolesnici su imali značajno kraće vreme hospitalizacije. Pored toga, ukoliko se intraoperativnom holangiografijom (IOH) pri LH ustanovi holedoholitijaza, ERCP sa EPT se može uraditi bez odlaganja.</p> / <p>Acute pancreatitis is an enzymatic inflammatory disease of the pancreas, with an incidence of around 17/100000 inhabitants. The most common etiological factors that are associated with this condition are biliary calculi (45%) and consumption of alcoholic beverages (35%). Less common causes include certain medications, hypertriglyceridemia, hyperkalemia, trauma, congenital factors and idiopathic pancreatitis (20%). According to the Atlanta International classification, acute pancreatitis can be manifested in a moderate, moderately severe and severe forms. Moderate forms of pancreatitis occur in 80%, characterized by pancreatic edema and have mild and short clinical course, with a mortality rate of 1%. The main goal of treatment of patients with acute pancreatitis in the first 24 hours of hospitalization is to facilitate complaints, determining the cause of pancreatitis and assessment of severity of the disease. Acute biliary pancreatitis is caused by calculosis of the gallbladder and / or bile ducts. The recommended treatment of biliary calculi, in order to prevent repeated attacks of moderate biliary pancreatitis, involves the removal of the gallbladder thru laparoscopic cholecystectomy with intraoperative cholangiography. If presence of bile duct calculi is established, an endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic papillotomy (EPT) and removes stones and detritus along the bile ducts is indicated, with the aim of ensuring the normal flow of bile into the duodenum. The aim of this study is the optimization of the order of application LH and ERCP with EPT, the identification of predictable indicators of choledocholithiasis, in order to shorten the length of hospitalization of patients with a moderate form of acute biliary pancreatitis. We conducted prospective case control study, with 100 patients involved, treated for moderate forms of acute biliary pancreatitis in the Emergency Center of the Clinical Center of Vojvodina, from 2011 to 2015, of which 80 made only with LH and 20 with LH at and ERCP with EPT . The analysis of clinical, ultrasound and laboratory findings identified 5 significant predictors of choledocholithiasis; direct and total bilirubin, alkaline phosphatase (AF), gamma glutiril transpepdidase (gamma GT) and C reactive protein (CRP), under which enabled the creation of a mathematical model for predicting choledocholithiasis, using the Support vector machines (SVM). It was found that pathological findings of these parameters indicate a significant choledocholithiasis, and LH is recommended as the first choice in patients in whom there are not present pathological predictors of choledocholithiasis. Thus treated patients had a significantly shorter hospital stay. In addition, if the intraoperative cholangiography (IOH) during LH show choledocholithiasis, ERCP with the EPT can be done without delay.</p>

<p>Akutni pankreatitis predstavlja zbirni pojam dinamičkih, lokalnih i sistemskih patofiziolo&scaron;kih procesa nastalih iznenadnim prodorom aktivnih litičkih pankreasnih enzima u žlezdani parenhim. Cilj istraživanja je da se Utvrditi senzitivnost difuzione sekvence magnetne rezonance (DWI) radi utvrđivanja morfolo&scaron;kih promena parenhima kod akutnog pankreatitisa. Poređenje difuzione mape i difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom i kod pacijenata sa morfolo&scaron;ki urednim parenhimom pankreasa na magnetnoj rezonanci. Utvrditi da li postoje statistički značajne razlike difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom u odnosu na pol. Utvrditi da li postoje statistički značajne razlike difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom u odnosu na godine. Odrediti prelomnu tačku difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom. Studija je bila prospektivnog karaktera i obuhvatilo je 30 ispitanika sa morfolo&scaron;ki urednim parenhimom pankreasa i 30 sa dijagnozom akutnog pankreatitisa unutar 72 sata od početka simptoma. Svi pacijenti su pregledani magnetnom rezonancom u Centru za radiologiju, Kliničkog Centra Vojvodine. Rezultati ukazuju da postoje razlike difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom i kontrolne grupe. Takođe smo dokazali da difuzioni koeficijent zavisi od pola i starosti i utvrdili smo prelomnu tačku difuzije za rano dijagnostikovanje akutnog pankreatitisa.</p> / <p>Acute pancreatitis is defined as cumulative term of dynamic local and general pathophysiological processes caused by sudden penetration of active lithic pancreatic enzymes in the glandular parenchyma. Goal of this research is to note the changes (sensitivity) in values of diffusion weighted images (DWI) in acute pancreatitis and to determine morphological changes in glandular parenchyma of pancreas. Comparation of DWI between patients with acute pancreatitis and patients with normal pancreatic parenchyma based on magnetic resonance (MRI). We also want to determine whether there were statistically significant differences of DWI in patients with acute pancreatitis in relation to sex and age. One of our goals also was to determine breakpoint of DWI as a sure sign of acute pancreatitis. This was prospective study and included 30 patients with morphologically healthy parenchyma of the pancreas (control group) and 30 with the diagnosis of acute pancreatitis &ndash; in first 72 hours of the onset of symptoms. All patients were examined on MRI in department of Radiology of Clinical Center of Vojvodina. Our results indicate that was a big difference of DWI between patients with acute pancreatitis and control group. We prove that DWI depends on the sex and age. 1,77x10-6mm/s2 was breakpoint which indicates acute pancreatitis.</p>

Die in den letzten Jahren erhobenen genetischen Befunden untermauern das Konzept, daß ein Ungleichgewicht von Proteasen und ihren Inhibitoren wesentlich an der Pathogenese der chronischen Pankreatitis beteiligt ist. Die Identifizierung von Mutationen im kationischen Trypsinogen bei Patienten mit hereditärer Pankreatitis hat das Verständnis der Erkrankung entscheidend beeinflußt. Der Nachweis von SPINK1-, CFTR- und PRSS1-Mutationen bei Patienten ohne Familienanamnese für eine Pankreatitis deutet darauf hin, daß auch die idiopathische Pankreatitis genetisch determiniert ist. Die bisher durchgeführten Studien legen nahe, daß die erblich bedingte chronische Pankreatitis eine genetisch heterogene Erkrankung ist, die in Abhängigkeit von den defekten Genen bzw. den zugrundeliegenden Mutationen einem autosomal dominanten, einem autosomal rezessiven oder einem komplexen Erbgang folgt. Das gehäufte Auftreten von SPINK1-Mutationen bei alkoholischer chronischer Pankreatitis ist ein Hinweis darauf, daß genetische Faktoren auch zur Suszeptibilität von primär nicht erblichen Formen der chronischen Pankreatitis beitragen. Im weiteren konnte gezeigt werden, daß genetische Dispositionsfaktoren auch bei der Pathogenese der tropischen Pankreatitis einen wesentlichen Stellenwert besitzen. Diese Daten stellen das Konzept der tropischen Pankreatitis als eigene, tropenspezifische Krankheitsentität in Frage. In der vorliegenden Arbeit wurde die Bedeutung genetischer Faktoren bei der Entstehung der hereditären und idiopathischen wie der alkoholischen Pankreatitis untersucht. Die vollständige Aufklärung der genetischen Ursachen wird vermutlich die Unterscheidung zwischen hereditärer und idiopathischer bzw. tropischer chronischer Pankreatitis obsolet werden lassen. Nach Ausschluß sekundärer Ursachen sollte auch bei Patienten ohne Familienanamnese eine Genanalyse auf Mutationen in den obengenannten Genen veranlaßt werden. / The recent discoveries of trypsinogen (PRSS1) and trypsin inhibitor (SPINK1) mutations in patients with hereditary and idiopathic chronic pancreatitis support the hypothesis that an inappropriate activation of pancreatic zymogens to active enzymes within the pancreatic parenchyma initiates the inflammatory process. Thus, pancreatitis may be the result of an imbalance of proteases and their inhibitors within the pancreatic parenchyma. Since the first description of inherited pancreatitis reported an autosomal dominant trait, hereditary CP was defined as an rare dominant inherited disease. Subsequently, the fact of familial clustering in one generation only, which indicates other inheritance pattern such as recessive or complex trait, was blinded out in the disease concept of hereditary CP for a long time. The Identification of PRSS1, SPINK1 and CFTR mutations in patients with so-called idiopathic chronic pancreatitis, however, shows that inherited cases of CP are much more frequent and that different mutations in different genes might lead to different inheritance pattern. Evaluation of patients with CP without an obvious predisposing factor should include genetic testing for mutations in the above mentioned genes even in the absence of a family history of pancreatitis. The finding of SPINK1 mutations in alcohol-induced pancreatitis indicates that genetic factors genetic factors may increase disease susceptibility to primary non-hereditary CP types. This work summarises the significance of genetic factors in the pathogenesis of hereditary and idiopathic as well as alcoholic chronic pancreatitis. Thus, the identification of further genes involved into the pathogenesis of inherited CP probably will also enhance our knowledge about more common types of CP such as alcoholic or tropical CP.