Attila Szepes

Autoimmune pancreatitis in Hungary: A multicenter nationwide study

Background: To date, most cases of autoimmune pancreatitis (AIP) have been reported from Japan. The aim of the present study was to assess the clinical features and management of AIP cases in Hungary. Methods: The demographics, clinical presentation, laboratory and imaging findings, extrapancreatic involvement, treatment response and recurrence were evaluated in the first 17 patients diagnosed with AIP in Hungary. Results: The mean age at presentation was 42.7 years (range: 16–74); 47% of the patients were women. New-onset mild abdominal pain (76%), weight loss (41%) and jaundice (41%) were the most common symptoms, with inflammatory bowel disease being the most frequent (36%) extrapancreatic manifestation. Diffuse pancreatic swelling was seen in 7 patients (41%) and a focal pancreatic mass in 8 (47%). Endoscopic retrograde cholangiopancreatography revealed pancreatic duct strictures in all study patients. The serum IgG4 level at presentation was elevated in 62% of the 8 patients in whom it was measured. All the percutaneous core biopsies (5 patients) and surgical specimens (2 patients), and 2 of the 4 biopsies of the papilla of Vater revealed the typical characteristic findings of AIP: a diffuse lymphoplasmacytic infiltration, marked interstitial fibrosis and obliterative phlebitis. Immunostaining indicated IgG4-positive plasma cells in 62% of the 8 patients in whom it was performed. Granulocytic epithelial lesions (GEL) were present in 3 patients. The patients without GELs were older (mean age 59 years), while those with GEL were younger (mean age 34 years), and 2 of 3 were female and had ulcerative colitis. A complete response to steroid treatment was achieved in all 15 patients. Because of the suspicion of a pancreatic tumor, 2 patients with focal AIP underwent partial pancreatectomy. One patient relapsed, but responded to azathioprine. Conclusions: This first Hungarian series has confirmed several previously reported findings on AIP. AIP with GEL was relatively frequent among our patients: these patients tended to be younger than in earlier studies and displayed a female preponderance with a high coincidence of ulcerative colitis. Performance of a percutaneous biopsy is strongly recommended. The response to immunosuppressive therapy was excellent.

The effects of somatostatin and octreotide on the human sphincter of Oddi

OBJECTIVE Somatostatin acts at different sites in the human gastrointestinal tract and generally inhibits the release and effects of many gastrointestinal hormones and neuropeptides. Together with its long-acting analogue octreotide, somatostatin is widely used in the treatment of hormone-producing tumours, variceal bleeding, etc., but multi-centre trials have failed to prove a beneficial effect in the treatment of acute pancreatitis or in the prevention of post-ERCP pancreatitis (pancreatitis following endoscopic retrograde cholangiopancreatography). The aim of the present work was to study the effects of somatostatin and octreotide on the human sphincter of Oddi by means of quantitative hepatobiliary scintigraphy (QHBS). METHOD Fifteen cholecystectomized patients were enrolled in the study, six in the somatostatin group and nine in the octreotide group. QHBS was performed initially with a standard protocol (baseline data), then repeated after 0.1 mg octreotide or a 250 microg bolus + 250 microg/h somatostatin administration. In the 60th min of QHBS, 0.5 mg glyceryl trinitrate (GTN) was administered sublingually. RESULTS QHBS demonstrated that both somatostatin and octreotide caused a marked impairment in the bile flow: the half-time of excretion (T1/2) over the common bile duct was significantly prolonged compared with baseline data (somatostatin group: common bile duct T1/2 180 min versus 59.7+/-31 min; octreotide group: common bile duct T1/2 140.9+/-60.5 min versus 30.7+/-11.7 min). Glyceryl trinitrate administration accelerated the transpapillary bile flow, with significant decreases in the elevated T1/2 in both groups. CONCLUSION Increased transpapillary flow induced by glyceryl trinitrate may be beneficial in the treatment of acute or post-ERCP pancreatitis.

Early ERCP and biliary sphincterotomy with or without small-caliber pancreatic stent insertion in patients with acute biliary pancreatitis: better overall outcome with adequate pancreatic drainage

Abstract Objective. To analyze the efficacy of pancreatic duct (PD) stenting following endoscopic sphincterotomy (EST) compared with EST alone in reducing complication rate and improving overall outcome in acute biliary pancreatitis (ABP). Methods. Between 1 January 2009 and 1 July 2010, 141 nonalcoholic patients with clinical, laboratory and imaging evidence of ABP were enrolled. Emergency endoscopic retrograde cholangiopancreatography (ERCP) was performed within 72 h from the onset of pain. Seventy patients underwent successful ERCP, EST, and stone extraction (control group); 71 patients (PD stent group) had EST, stone extraction and small-caliber (5 Fr, 3-5 cm) pancreatic stent insertion. All patients were hospitalized for medical therapy and jejunal feeding and were followed up. Results. The mean age, Glasgow score, symptom to ERCP time, mean amylase and CRP levels at initial presentation were not significantly different in the PD stent group compared to the control group: 60.6 vs. 64.3, 3.21 vs. 3.27, 34.4 vs. 40.2, 2446.9 vs. 2114.3, 121.1 vs. 152.4, respectively. Complications (admission to intensive care unit, pancreatic necrosis with septicemia, large (>6 cm) pseudocyst formation, need for surgical necrosectomy) were less frequent in the PD stent group resulting in a significantly lower overall complication rate (9.86% vs. 31.43%, p < 0.002). Mortality rates (0% vs. 4.28%) were comparable, reasonably low and without any significant differences. Conclusions. Temporary small-caliber PD stent placement may offer sufficient drainage to reverse the process of ABP. Combined with EST the process results in a significantly less complication rate and better clinical outcome compared with EST alone during the early course of ABP.

Successful endoscopic clipping in the early treatment of spontaneous esophageal perforation

Barogenic esophageal injury or Boerhaave syndrome is an esophageal perforation entailing very high mortality and morbidity. Endoscopic techniques have been introduced in the treatment of various types of esophageal perforation. This report describes the first patient who underwent a successful endoscopic clipping involving sealing of a transpleural esophageal rupture within 24 hours of the onset of symptoms.

Humoral mechanisms and clinical aspects of biliary tract motility

This review is intended to summarize current information on neurohumoral regulation of the gallbladder and sphincter of Oddi motility under both physiological and pathological circumstances with emphasis on Hungarian contributions to todays knowledge. The mechanism of action of neurohumoral agents that interact on these segments of the biliary tract, and the explored details of the stimulation-contraction/relaxation coupling process of these substances, will be discussed. A modified classification of biliary tract motility disorders with new diagnostic and therapeutic approaches will also be provided. This information will aid understanding of the pathogenesis of motor disorders of the gallbladder and sphincter of Oddi, and will indicate possibilities for pharmacological exploitation in the treatment of diseases resulting from biliary tract motility abnormalities.

Endoscopic retrograde pancreatography: When should we do it?

Endoscopic retrograde pancreatography (ERP) is an accurate imaging modality in the diagnosis of pancreatobiliary diseases. However, its use has been substantially reduced due to the invasiveness of procedure, the risk of complications and the widespread availability of non-invasive cross-section imaging techniques (computed tomography, magnetic resonance imaging, and endoscopic ultrasound). Since the introduction of endoscopic sphincterotomy, ERP has transformed from diagnostic method to an almost exclusively therapeutic procedure. Pancreatic duct injection substantially increased the risk of post-ERP pancreatitis (1.6%-15.7%); therefore, according to international guidelines ERP is recommended only in cases where biliary intervention is required. However, the role of ERP in the management of pancreatic diseases is currently not clearly defined, but in some cases the filling of pancreatic duct may provide essential information complementing the results of non-invasive imaging techniques. The aim of this publication is to systematically summarize the literature dealing with the diagnostic yield of ERP. We would like to define the precise indications of ERP and overview a diagnostic protocol of pancreatic diseases depending on international guidelines and the opinion of Hungarian experts, because it may improve the diagnostic accuracy, minimize of burden of patients and reduce the risk of procedure related complications.

Diagnosis of gallbladder dyskinesia by quantitative hepatobiliary scintigraphy

Aim: The aim of the present study was to develop a new pharmacologic method during hepatobiliary scintigraphy by which patients with functional and organic forms of gallbladder (GB) dysfunction can be differentiated. Methods: Quantitative hepatobiliary scintigraphy (QHBS) was performed on 31 patients with impaired GB motility selected by cerulein-augmented ultrasonography. Nineteen patients had acalculous biliary pain (ABP) and suspected GB dyskinesia, 6 patients had celiac disease, and 6 patients had type II diabetes mellitus. Sixty minutes after the isotope administration, 1 ng/bwkg/min cerulein (CCK10) was infused for 10 minutes, and then from the 90th minute, an equivalent dose of CCK10 was infused in the presence of 0.5 mg sublingual glyceryl trinitrate (GTN) in 12 or placebo in 7 consecutive patients. The GB ejection fraction (GBEF) was calculated repeatedly in time periods from 60 to 90 and from 90 to 120 minutes. Results: In the majority of patients with ABP and suspected GB dyskinesia, CCK10 and GTN coadministration normalized the previously impaired GB-emptying. When the cumulative results of all 12 patients were calculated, we demonstrated significant differences (P = 0.003) in the GBEF between the first (CCK10) versus the second (CCK10 plus GTN) stimuli: 19 ± 11% versus 40 ± 17%, respectively. In contrast, in 12 patients with celiac sprue and diabetes mellitus, no differences in the GBEF were detected when the first (CCK10 alone) versus the second (CCK10 plus GTN) stimuli was compared: 21 ± 10% versus 22 ± 13%, respectively. Finally, placebo and CCK10 coadministration in 7 consecutive patients with ABP and suspected GB dyskinesia did not influence the GBEF as compared with CCK10 alone: 13 ± 9% versus 15 ± 10%, respectively. Conclusion: GTN and CCK10 coadministration induces a significant improvement of the GBEF in patients with GB dyskinesia. The application of this new pharmacologic test during QHBS permitted the noninvasive separation of those patients with secondary impaired GB-emptying as a result of GB dyskinesia from those with primary forms of GB hypokinesia.

Effect of nitric oxide on gallbladder motility in patients with acalculous biliary pain: A cholescintigraphic study

The aim of the present study was to evaluate the influence of the exogenous nitric oxide donor glyceryl trinitrate on cerulein-induced gallbladder contraction in patients with acalculous biliary pain. Quantitative hepatobiliary scintigraphy was performed on 33 patients. From the 60th min cerulein (1 ng/kg body wt/min for 10 min intravenous) then from the 90th min the same dose of cerulein plus glyceryl trinitrate (0.5 mg sublingually) (21 patients) or placebo (12 patients) were administered and the gallbladder ejection fraction was measured repeatedly. After the first dose of caerulein, the gallbladder ejection fraction was less than 35% in 23 of 33 patients (nonresponders), while it was more than 35% in the remaining 10 patients (responders). After the second dose of cerulein in 16 nonresponder patients glyceryl trinitrate administration significantly increased the previously impaired gallbladder ejection fraction while in 7 nonresponder patients placebo administration had no effect. In conclusion, normalization of the gallbladder ejection fraction in the majority of patients following glyceryl trinitrate administration suggests that impairment of gallbladder emptying is caused by a functional motility disorder rather than any organic disease.

The effect of endoscopic sphincterotomy on the motility of the gallbladder and sphincter of Oddi in patients with acalculous biliary pain syndrome

INTRODUCTION Sphincter of Oddi dysfunction usually occurs after cholecystectomy, but it can sometimes be detected in patients with intact gallbladder too. The diagnostic value of the non-invasive functional tests is not established in this group of patients and the effects of sphincterotomy on transpapillary bile outflow and gallbladder motility are unknown. AIMS The aim of this study was to determine the effect of endoscopic sphincterotomy on the gallbladder ejection fraction, transpapillary bile outflow and the clinical symptoms of patients with acalculous biliary pain syndrome. PATIENTS AND METHODS 36 patients with acalculous biliary pain syndrome underwent quantitative hepatobiliary scintigraphy, and all of them had decreased cholecytokinin-induced gallbladder ejection fraction. The endoscopic manometry of the sphincter of Oddi showed abnormal sphincter function in 26 patients who were enrolled the study. Before and after endoscopic sphincterotomy all patients had ultrasonographic measurement of cholecystokinin-induced gallbladder ejection fraction with and without nitroglycerin pretreatment and scintigraphy was repeated as well. The effects of sphincterotomy on gallbladder ejection fraction and transpapillary biliary outflow were evaluated. In addition, changes in biliary pain score with a previously validated questionnaire were also determined. RESULTS All 26 patients had decreased gallbladder ejection fraction before sphincterotomy measured with scintigraphy (19+18%) and ultrasound (16+9.7%), which was improved after nitroglycerin pretreatment (48.2+17%; p<0.005). Detected with both methods, the ejection fraction was in the normal range after sphincterotomy (52+37% and 40.8+16.5%), but nitroglycerin pretreatment failed to produce further improvement (48.67+22.2%, NS). Based on scintigraphic examination sphincterotomy significantly improved transpapillary biliary outflow (common bile duct half time 63±33 min vs. 37±17 min; p<0.05). According to results obtained from questionneries, 22 of the 26 patients gave an account of significant symptom improvement after sphincterotomy. CONCLUSIONS Endoscopic sphincterotomy improves cholecystokinin-induced gallbladder ejection fraction, transpapillary biliary outflow as well as biliary symptoms in patients with acalculous biliary pain syndrome and sphincter of Oddi dysfunction. Cholecystokinin-induced gallbladder ejection fraction with nitroglycerin pretreatment, measured with ultrasonography can be useful to select a subgroup of patients who can benefit from sphincterotomy.

Enhanced Filling and Cholecystokinin-Induced Emptying of the Human Gallbladder after Glyceryl Trinitrate Administration: A Scintigraphic Sign of Functional Cystic Duct Syndrome

The distinctive features of cystic duct syndrome are acalculous biliary pain (ABP) with impaired gallbladder (GB) filling, emptying, or both. The mechanism of ABP pain has been explained in theory by exaggerated GB contraction, which was intended to overcome a functional cystic duct obstruction or GB dyskinesia. However, no human data lend support to this pathomechanism. The authors present new scintigraphic features suggestive of functional cystic duct obstruction in humans.