Endoscopy in idiopathic recurrent pancreatitis. Endoscopy for Idiopathic recurrent acute pancreatitis - the truth in between. Markus M.

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1 1456 Endoscopy for Idiopathic recurrent acute pancreatitis - the truth in between APA Miami Markus M. Lerch Medizinische Klinik der königlichen Universität Greifswald 1859 Disclosure: consultancy to Roche, AstraZeneca, Sanofi-Aventis, Alpinia, Abbott, Novartis, Lilly, DFG, German ancer Foundation, NIH Department: 850 therapeutic ERP, 1025 EUS Department of Medicine A University Medicine Greifswald Natural ourse of recurrent/chronic Pancreatitis - Stage 1 (early) Stage 2 Stage 3 Pain Serum Enzyme Elevation Exocrine Pancreatic Function years Statement: Recurrent Acute Pancreatitis Recurrent acute pancreatitis is defined as recurrent episodes of pancreatitis - regardless of etiology - with a greater threefold rise of serum amylase or lipase in combination with abdominal pain but in the absence of impaired exocrine or endocrine function or morphological signs of chronic pancreatitis. Recurrent acute pancreatitis is often diagnosed in early childhood in patients suffering from familial or idiopathic chronic pancreatitis. Evidence 3b Voting Result consensus conference: Votes: 40 Agreement: 71% Prague 2012: onsensus Guidelines on genetic testing and counselling in Inherited Diseases of the Pancreas Modified according to R Ammann, Schweiz Rundsch Med Prax. 1970; 59: In association with germline mutations Hereditary Pancreatitis (PRSS1 / trypsin mutations) Hereditary pancreatitis is clinically difficult to distinguish from other forms and varities of pancreatitis but for age of onset In association with occult biliary disease (microlithiasis/sludge; bile crystals) (SOD type I, II or III) 14 year old girl with chronic pancreatitis and R122H-mutation 48 year old women with chronic Pancreatitis and R122H-mutation HP typically begins as irap and invariably progesses to P 1

2 Endoscopic treatment of hereditary pancreatitis eppa EP et al. Hereditary pancreatitis: endoscopic and surgical management. J Gastrointest Surg. 2013;17: ase series: 87 patients (54 with confirmed mutations) ; 85 patients underwent 263 endoscopies 72% sphincterotomy; 49% stone removal; 82% duct stenting; 28% surgery (19 resection / 18 drainage) Surgery 9.1 years to symptom recurrence; endoscopy 3.4 years Dever J et al. J. lin. Gastroenterol 2010;44:46-51 ase series: 21 patients, 87 therapeutic ERPs (mean 4); follow up 5 y; ~age 15y; 11 of 12 surgical with drainage procedures required additional ERP; pain score from 8.3 to 3.2 Hospital visits from 5.7 to 1.9; Oxycodon from 39 to 34 mg/day; 3% complication from ERP Endoscopic treatment of chronic pancreatitis Author n reduction in pain morbidity Follow-up (months) Kozarek % 12% 8 remer % 5 % 37 inmoeller % ahsin % 10 % 16 Rösch % 13 % 60 Endoscopic treatment induces short term pain relief in at least 2/3 of cases. No controlled studies exist. Endoscopic versus surgical drainage of pancreatic duct stenosis in chronic pancreatitis D.L. ahen New Engl J Med 2007; 356: D.L. ahen Gastroenterology. 2011;141: randomised trial to compare endoscopic versus surgical treatement for chronic pancreatitis; n = 39, 19 endoscopic therapy, 20 pancreatikojejunostomie Surgery: 100 % Drainage-Operation Endoscopic Intervention: 84 % ESWL 100 % EPT + Stent Follow-Up: 2 years Mittlerer Izbicki Schmerz Score 19 Endoscopy Surgery p< Follow-up [Monate] Surgery is superior to endoscopy in terms of longterm pain relief. Neither probably changes disease progression. Genetic Risk Factors in Idiopathic Pancreatitis No known mutation: 30-45% arboxy peptidase A1: 3% vs. 0.1% alcium sensing Receptor: 19% vs. 10% ationic trypsinogen (PRSS1): 4-10% vs. 0% SPINK1: 15-25% vs.1-1.6% hymotrpsinogen : 5% vs.1% FTR: 25-30% vs.10-15% Most germline mutations represent risk factors and do not infer causality in an individual patient (e.g. FTR) In association with germline mutations: poor evidence and only for late stages of the disease (P); not really for irap In association with occult biliary disease (microlithiasis/sludge; bile crystals (type I, II or III) Sphincterotomy for mircrolithiasis in IRAP Ros E, et al. Gastroenterology. 1991;101: ase series: 51 patients IRAP, 24 relapsing; 67% endoscopic microscopic stones/crystals; 73% in cholecystectomized gallbladder; Prevention of gallstone-induced relaps in 13 by Urso (44 months) and in 17 of 18 by cholecystectomy (36 months) Thorboll J. et al. Scand. J. Gastroenterolol; 2004; 39: ase series: 52.4 % of patients with acute pancreattiis of unknown etiology with negative transabdominal ultrasound have microlithiasis on EUS. Vazques-Iglesias JL et al Surg. Endoscopy 2004; 18: ase series: 88 patients with sphincterotomy to prevent recurrence of biliary pancreatitis with gallbladder in situ. Recurrence rate after EPT 2.2% (median 51m) 2

3 What is the role of cholecystectomy after endoscopic sphincterotomy? Study, year, country Methods Grade N Re-admissions after previous ER/ES without / delayed cholecystectomy after MAP (biliary pancreatitis, cholecystitis, colics) Schachter Griniatsos Ito 14 (12%) (2,5,7) Nebiker, Sinha akker 8 (14%) (2,2,4) Teoh 5 (7%) (1,4,0) Heider Gislason in patients after biliary pancreatitis 46 (42%) 109 (cholecystitis, colics, with MAP and SAP 2003 (1,20,25) Hammerstrom pancreatitis) 1 (2%) 64 in 6 % with MAP and SAP 2003 (1,0,0) Hui 4 (7%) 58 with MAP and SAP 2004 (3,1,0) Kaw 5 (15%) 34 with MAP and SAP 2002 (2,1,2) Uomo 18 (69%) 26 with MAP and SAP 1997 (5,0,13) Vazquez 2 (2%) 88 with MAP and SAP 2004 (2,0,0) 27 (6%) TOTAL 484 (5,11,11) Readmission with biliary pathology after ER/papillotomy Remark Stratification of IRA by etiology In association with germline mutations: poor evidence and only for late stages of the disease (P); not really for irap Good evidence for benefit when detected by EUS (bile microscopy of more questionable use); gallbladder surgery possibly more effective (type I, II or III) Pancreas Divisum SHIP study Greifswald Population based study (4500 total) 995 secretin (1U/kg) stimulated MRP; 457 females, 538 males mean age 51.9 ± 13.4 years Navigator-triggered T2-weighted 3D turbo-spin-echo MRP; 1.5T MR scanner. Two reader evaluation ülow R. et al. Radiology 2013 submitted Pancreas Divisum SHIP study Greifswald 93.2% smrp diagnostic Interobserver reliability: kappa1 = (P>0.001), 95% I (0.906, 0.930) kappa2 = (P>0.001), 95% I (0.761, 0.801) Nonvariant pancreatic duct types 90.4 % (n=838/927) Pancreas divisum was identified in 9.6 % (n=89/927) Abnormalities of main pancreatic duct 2.4% Side branch dilatation 16.6% Pancreatic cysts 27.7% none more common in pancreas divisum (P=0.122; P= 0.152; P= 0.741). ülow R. et al. Radiology 2013 in press Pancreas Divisum and Pancreatitis: Evidence of therapy Surgery: Sphinctero-plasty of minor papilla (88/100) clinical improvement in 74% ARP vs. 38% in pain group Endoscopic therapy: 8 observational studies; total of 435 patients; clinical improvement (total): 64,8%; efficiency: ARP 80.9% > P 58.6% > pain 46.9 %: complication rate 15% 1 controlled study on 19 patients with irap and PD (2 episodes). 10 stents in minor papilla; follow up 28.6 m; RAP in 1; 9 controls; follow up 31.5 m; RAP in 7, p<0.05) Lans JI et al. Gastrointest Endosc 1992;38:430-4; Lehman G. et al. Gastrointest. Endoscopy 1993;39:1-8; otton P et al. Gut 1980; 21: ; Klein et al. Gastrointest Endosc 2004;419-25; orak GD et al.pancreas 2009;38: ; Saltzman Gastrointest Endosc 2006;64:712-15; arthet Eur M. et al. J Gastroenterol Hepatol 1995;7:993-8 stages of the disease stages of the disease (P); not really for irap Good evidence for benefit when detected by EUS (bile microscopy of more questionable use); gallbladder surgery possibly more effective : controversial whether PD (and which subtype) causes irap. No good evidence on whether stent placement or sphincterotomy is superior to sham treatment. (type I, II or III) 3

4 lassification sphincter of Oddi dysfunction Typ I: pain in right upper quadrant (biliary type), 2x elevated liver enzymes (pancreatic enzymes) AND bile duct dilatation (10-12mm) possibly microlithiasis or sphincter stenosis after gallstone passage Typ II: pain with pancreatic/liver enzyme elevation OR bile-duct dilatation possibly microlithiasis or sphincter stenosis after gallstone passage Typ III: pain without any of the above. mostly diagnosed by Sphincter monometry E.S. orazziari, P.. otton Rome Foundation Diagnostic Algorithms Gallbladder and Sphincter of Oddi Disorders. AG 2010;105, Image source Johns Hopkins Sphincter of Oddi dysfunction Fischer M. et al. Pancreatology 2010;10: ase series: 1241 patients; ERP with SOM diagnostic in 65.8 %. 40.8% SOD; 18,8% Pancreas divisium; 92% amenable to endoscopic therapy; No outcome reported. Indianapolis group. oté GA et al. Gastroenterology 2012 Dec;143(6): Randomization of 69 patients with SOD; Reccurent AP in 48.5% after bile-duct papillotomy; 47.2% after bile/pancreatic duct papillotomy (NS). In patients with normal SOM, 27.3% had recurrent pancreatitis after bile duct and 11.1% after sham intervention. In SOD versus normal SEM, HR 4.3 for recurrent acute pancreatitis Sphincterotomy is, at best, moderately effective in reducing recurrence of irap in patients with SOD Textmed entity search engine Statistics on sphincter of Oddi dysfunction Population of Germany 82 Mio Nebraska Minnesota Missouri Michigan Indiana Alabama Louisiana Pennsylvania Maryland holecystectomy Acute and chronic pancreatitis Hospital procedures (total) 49 Mio ER/ERP ERP Manometry of the oesophagus Manometry of the sphincter of Oddi 29 German federal statistics office 2011 EPISOD study PI: P.. otton stages of the disease stages of the disease (P); not really for irap Good evidence for benefit when detected by EUS (bile microscopy of more questionable use); gallbladder surgery possibly more effective linicaltrials.gov Identifier: NT ondition Intervention Phase Sphincter of Oddi Dysfunction Procedure: Pancreatic Sphincterotomy Procedure: Pancreatic and iliary Sphincterotomy Procedure: ERP Phase 3 : controversial whether PD (and which subtype) causes irap. No good evidence on whether stent placement or sphincterotomy is superior to sham treatment. Some patients with (type I/II) SOD may have occult gallstone disease (see above). Whether type II/III SOD benefits from endoscopic therapy will be established by the soon to be announced results of the EPISOD study. 4

5 Julia Mayerle Peter Simon Ali Aghdassi Jonas Scheiber Georg eyer Uli Weiss 602 patients randomized to either rectal Indometacin (50mg supp) or placebo 82 % sphincter of Oddi dysfunction. Outcome ERP-induced pancreatitis: 3x lipase after 24h, at least two nights in hospital 5

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