CHRONIC PANCREATITIS CONSERVATIVE TREATMENT, ENDOSCOPY OR SURGERY?

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Endoscopy 2006 Update and Live Demonstration Berlin, 04. 05. Mai 2006 CHRONIC PANCREATITIS CONSERVATIVE TREATMENT, ENDOSCOPY OR SURGERY? J. F. Riemann A. Rosenbaum Medizinische Klinik C, Klinikum Ludwigshafen ggmbh (Gastroenterologie, Hepatologie und Diabetologie)

CHRONIC PANCREATITIS COURSE OF DISEASE Prospective study over 20 years N= 254; chronic pancreatitis (163 alcoholic CP, with calcifications in 145) Follow-up 10,4 ys. (median) In 85% of pts. with calcifications continued improvement after 4,5 ys. (median) In 47% of 163 pts. with alcoholic CP surgery necessary 50-60% of pts. with CP develop complications which require endoscopic or surgical intervention Ammann, Gastroenterology 1984 Ammann, Intern Med 2001

CHRONIC PANCREATITIS PAIN Local inflammation of pancreatic tissue with expression of neuropeptides (e.g. substance P) Elevation of pressure in pancreatic duct by stricture Pancreatic compartment syndrome Local compression by pseudocysts Extrapancreatic reasons: Metereorism (steatorrhea) Peptic ulcer Di Sebastiano et al., Gut 2003

CHRONIC PANCREATITIS COMPLICATIONS Pancreatic duct strictures Pancreatic stones Choledochal duct strictures Pseudocysts Inflammatory swelling of pancreatic head Duodenal or colonic stenoses Elevated pressure of portal vein GI- bleeding Exo- und endocrineous insufficiency Cancer + Symptoms = Endoscopic therapy

CHRONIC PANCREATITIS THERAPY - GOALS - 1. Analgesia 2. Therapy of exocrine insufficiency 3. Therapy of endocrine insufficiency Lankisch, Internist 2005

CHRONIC PANCREATITIS MANAGEMENT COMPLICATIONS PAIN MALDIGESTION DIABETES Interventional endoscopy Surgery Alcohol abstinence Enzymes / Diet Spasmolytics Analgetics (NSAID etc.) Surgery Enzymes Diet Insulin

CHRONIC PANCREATITIS PAIN MANAGEMENT Conservative Interventional endoscopy Surgery

CHRONIC PANCREATITIS PAIN CONSERVATIVE TREATMENT - First: exclusion of treatable complications Strict abstinence from alcohol Analgetics (NSAID, non opioid) Celiac block (CT- or EUS- guided) Drug addiction must be avoided

CHRONIC PANCREATITIS ENDOSCOPIC THERAPY - GUIDELINES Concerning the endoscopic therapy of chronic pancreatitis only few randomized controlled prospective trials are available in international literature No long-term results exist regarding the outcome of endotherapy Recommendations concerning therapy of strictures of the pancreatic or choledochal duct and pseudocysts are based on expert opinions and uncontrolled trials DGVS-Leitlinien, Z Gastroenterol 1998

CHRONIC PANCREATITIS Ludwigshafen - Registry Retrospective and prospective (since 1998) registry n=291 patients with chronic pancreatitis Endoscopic therapy: n= 262 patients Follow-up: Median 84 months (6-168 Months) Hospital stays per patient (re-therapy): Median 4,2 (1-15) Endoscopic intervention Stenting of pancreatic duct EST Bile duct stenosis Pseudocysts N 89 191 60 38

ENDOSCOPIC THERAPY CP SPHINCTEROTOMY Endosocpic sphincterotomy to pancreatic duct in patients with chronic pancreatitis own data (n=191)* Ell (n=118)** Success 187 (96,1 %) 116 (98 %) Complications 9 (4,7 %) 5 (4,2 %) Follow-up 16-160 months 42 months Re-EST necessary 23 (12 %) 18 (15 %) *Ludwigshafener Pankreatitisregister 2006 **Gastrointest Endosc 1998

ENDOSCOPIC THERAPY CP PANCREATIC DUCT STRICTURE N = 89; men/women: 51/38; median age: 55,3 ys. 2,6 stents/patient; duration of stenting 254 days Follow-up: 78 (9-164) months 12 months 24 months 40 months 70 months clearly improved (%) 55 45 42 40 moderately improved (%) 16 18 18 20 No further stenting: 33 (38%) Surgery: 21 (24%) Own data, Ludwigshafener Pankreatitisregister 2006

ENDOSCOPIC THERAPY CP PANCREATIC DUCT STONES / ESWL Metaanalysis N = 588, 17 trials (1989-2002) Interventional endoscopic therapy plus ESWL N = 80, F/U 40 Mon. Follow-up: mean 20 mon. (6-72) Results (Effect size*): Stonefree 0,74 Improvement of pain 0,62 (*large effect: Effect size 0,5) Guda et al., J Pancreas (Online) 2005

Results of endoscopic interventional therapy ENDOSCOPIC THERAPY CP PANCREATIC DUCT STRICTURE/ LITERATURE Author Cremer 1991 Binmoeller 1995 Smits 1995 Jakobs 1999 Rösch 2002 Delhaye 2004 Gabrielli 2005 Farnbacher 2006 n 75 93 49 27 1018 56 22 96 Follow-up (Months) 37 39 34 44 59 173 72 35 Clinically improved (%) 94 74 82 56 86 66 55 59

ENDOSCOPIC THERAPY CP REFRACTORY PANCREATIC STRICTURE Prospective trial n=19; Refractory stricture of pancreatic head Multiple stenting of pancreatic duct (median 3 stents) Mean Follow-up: 38 months Costamagna et al., Endoscopy 2006

(mean follow-up: 4,9 Jahre) Intensity Endotherapy OP of pain (n=758) (n=238) none light ENDOSCOPIC THERAPY CP ENDOTHERAPY VS. SURGERY 87% 79% middle 10% 15% strong 3% 3% Rösch T et al., Endoscopy 2002

PANCREATIC DUCT STRICTURE SURGERY VS. ENDOTHERAPY N = 140 Prospective controlled (partly randomized) trial Obstruction of pancreatic duct an pain All (N=140) Randomized (N=72) *endoscopic intervention (without ESWL) EI* (%) CI** (%) EI (%) CI (%) **surgical intervention Analgesia 14,3 36,9 15 33,8 Weight gain 26,9 52,1 28,6 47,2 Dite et al., Endoscopy 2003

ENDOSCOPIC THERAPY CP BILE DUCT STRICTURE / PLASTIC STENTS Long-term results of bile duct stenting in CP n=60, Follow-up: 86 months (mean) Success n=29 (48%) 0 100% NB: Since 2001 programmed implantation of mulitple stents (Medían 3,2 Stents/Pat.) Success-rates rising!! Eickhoff, 2006 No success n=31 (52%) Stent in situ / improved n=11 (44 (4-120) Mon.) Surgery / improved n=13 (11,5 (1-45) Mon.) Stent in situ / death* * n=7 *(not from cholangitis)

ENDOSCOPIC THERAPY CP BILE DUCT STENTS / RISK OF OCCLUSION Retrospective trial (1996 1999) N = 61 Pat. with CP Risk factors for unsuccessful stenting of common bile duct Exocrine pancreatic insuff. Endocrine pancreatic insuff. Calcifications of pancreatic head Swelling of pancreatic head Ongoing alcohol abuse Duration of illness RR (95% CI) 3,97 (1,2-13,2) 1,12 (0,36-3,5) 17,3 (4,1-74) 1,01 (0,29-3,45) 0,58 (0,31-1,09) 1,01 (0,91-1,23) p 0,024 0,841 <0,001 0,992 0,0882 0,83 Kahl et al., Am J Gastroenterol 2003

ENDOSCOPIC THERAPY CP BILE DUCT STRICTURE / MULTIPLE STENTING Autor n Follow-up (Mon.) Removal of stricture (%) Draganov 2002 9 48 44 Catalano 2004 12 46 100 Pozsar 2004 29 12,1 60

ENDOSCOPIC THERAPY CP BILE DUCT STRICTURE / METAL STENTS Author n Techn. success Long-term success Complications Follow up (months) Deviere 1994 20 100% 90% (18) 10% 33 Van Westerloo 2000 15 100% 80% (12) 13% 14 Kahl 2003 3 100% 100% (3) 0% 18-57 Van Berkel 2004 13 100% 69% (9) 8% 50 Eickhoff 2006 8 100% 37,5% (3) 62% 12-64 Wallstent

ENDOSCOPIC THERAPY CP PSEUDOCYSTS / LITERATURE n transpapillary/ Success- Complications Relapse transgastral/ rate transduodenal Cremer 1989 33 0 / 11 / 22 96 % 6 % 12 % Sahel 1991 43 0 / 3 / 40 93 % 11 % 5 % Barthet 1995 30 30 / 0 / 0 77 % 13 % 10 % Binmoeller 1995 53 29 /? /? 77 % 11 % 22 % Cahen 2005 92 25 / 33 / 21 71 % 34% 5 % Own data 2006 38 6 / 13 / 6 88 % 7 % 12 %

ENDOSCOPIC THERAPY CP PSEUDOCYSTS - PROSPECTIVE TRIAL Prospective trial N = 99 patients with pancreatic pseudocysts Comparison of short-term and long-term results: Conventional vs. EUS-guided drainage Follow-up: 6 months Method N Short-term success Long-term success Complications Conventional 53 94% 91% 18% EUS-guided 46 93% 84% 19% n.s. n.s. n.s. Kahaleh et al., Endoscopy 2006

CHRONIC PANCREATITIS SURGERY Severe chronic pancreatitis of head With duodenal stricture With extensive calcifications Multiple strictures of pancreatic duct / multiple stones Failure of conservative and interventional endoscopic therapy (regarding pain,, large pseudocysts,, inner fistulas, bleeding pseudoaneurysm) Suspected cancer Pankreas-Ca DGVS-Leitlinien, Z Gastroenterol 1998 Lankisch, Internist 2005

CONCLUSION More than half of all patients with CP require interventional endoscopic therapy or surgery because of complications Conservative treatment is fundamental but must not lead to drug addiction Endoscopic therapy reduces pain caused by strictures and pseudocysts Surgery is indicated if conventional and endoscopic therapy fails

TEAM APPROACH Adequate management? TEAM of gastroenterologist and surgeon INDIVIDUAL THERAPY: First step: Endoscopic therapy Second step: Surgery Traverso, Bern, 2000