CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2012;10:795–802
Endoscopic Therapy Is Effective for Patients With Chronic PancreatitisBRIDGER CLARKE,* ADAM SLIVKA,* YUTAKA TOMIZAWA,* MICHAEL SANDERS,* GEORGIOS I. PAPACHRISTOU,*,‡
DAVID C. WHITCOMB,*,§ and DHIRAJ YADAV*
*Department of Medicine, and §Department of Human Genetics, University of Pittsburgh; and ‡Veterans Administration Hospital, Pittsburgh, Pennsylvania
This article has an accompanying continuing medical education activity on page e63. Learning Objectives—At theend of this activity, the successful learner will be able to assess the effectiveness of endoscopic therapy and surgery
as well as the natural history in medically managed patients with chronic pancreatitis.
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See editorial on page 803.
BACKGROUND & AIMS: Endoscopic therapy (ET) fre-quently is used to treat patients with painful chronic pancreatitis (CP),but little is known about outcomes of patients for whom ET was notsuccessful who then underwent surgery, or outcomes after ET com-pared with only medical treatment. We evaluated use and long-termeffectiveness of ET in a well-defined cohort of patients with CP.METHODS: We analyzed data from 146 patients with CP whoparticipated in the North American Pancreatitis Study 2 at the Uni-versity of Pittsburgh Medical Center from 2000 to 2006; 71 (49%)patients received ET at the University of Pittsburgh Medical Center.Success of ET and surgery were defined by cessation of narcotictherapy and resolution of episodes of acute pancreatitis. Diseaseprogression was followed up from its onset until January 1, 2011(mean, 8.2 � 4.7 y). RESULTS: Patients who underwent ET hadmore symptoms (pain, recurrent pancreatitis) and had more complexpancreatic morphology (based on imaging) than patients who re-ceived medical therapy. ET had a high rate of technical success (60 of71 cases; 85%); its rates of clinical success were 51% for 28 of 55patients for whom follow-up data were available (mean time, 4.8 �3.0 y) and 50% for 12 of 24 patients who underwent surgery afterreceiving ET. Patients who responded to ET were significantly older,had a shorter duration of disease before ET, had less constant pain,and required fewer daily narcotics than patients who did not respondto ET. Among the 36 symptomatic patients who received medicaltherapy and were followed up for a mean period of 5.7 � 4.1 years,31% improved and 53% had no change in symptoms; of these, 21%underwent surgery. CONCLUSIONS: ET is clinically success-ul for 50% of patients with symptomatic CP. When ET is notuccessful, surgery has successful outcomes in 50% of patients.ymptoms resolve in 31% of symptomatic patients who receivenly medical therapy.
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Chronic pancreatitis (CP) is a progressive inflammatorydisease of the pancreas characterized by destruction of
pancreatic parenchyma and subsequent fibrosis, leading to exo-crine and/or endocrine insufficiency.1 Abdominal pain is a
rominent symptom in many CP patients and often is debili-ating. An important mechanism for pain in CP is intraductalypertension as a result of pancreatic duct (PD) obstruction
rom stones or strictures.2– 4 Other suggested mechanisms ofpain include ongoing inflammation, peripheral or central neu-ropathic processes, and pancreatic or peripancreatic complica-tions (eg, pseudocysts, biliary stricture, compression of sur-rounding structures).3–5
Endoscopic and surgical treatments in CP patients are pur-sued to relieve pain and address local complications.6 –32 Al-hough effectiveness of endoscopic therapy (ET) has been eval-ated in several studies, most were limited by small numbers ofatients, incomplete follow-up evaluation, and lack of a medi-ally managed control arm.6 –20 Moreover, most studies havesed pain as an indication for and outcome of ET and do notresent a comprehensive evaluation of ET for all indications
eg, recurrent acute pancreatitis [RAP], PD leak, biliary stricture,nd so forth). There are also a paucity of data describing the usef ET within a cohort of CP patients. There are few studiesomparing outcomes of surgery with ET, and existing data onurgical treatment focuses mainly on patients who have notndergone prior ET.21–32 Little data are available on the out-
comes of pancreatic surgery after failed ET, which is morerepresentative of the current clinical practice.
We evaluated the use, effectiveness, and long-term clinicaloutcomes of ET in a well-phenotyped cohort of CP patients andcompared it with patients who were managed medically.
MethodsPatient CohortThe North American Pancreatitis Study 2 (NAPS2) was a
multicenter study in which 540 CP and 460 RAP patients prospec-tively were enrolled between 2000 and 2006 from 19 secondaryand tertiary referral centers with interest in pancreatic diseases in
Abbreviations used in this paper: CP, chronic pancreatitis; ERCP,endoscopic retrograde cholangiopancreatography; ET, endoscopictherapy; NAPS2, North American Pancreatitis Study 2; PD, pancreaticduct; RAP, recurrent acute pancreatitis; UPMC, University of PittsburghMedical Center.
796 CLARKE ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 10, No. 7
the United States between 2000 and 2006.33 The inclusion criteriaor CP was presence of definitive changes on imaging studiesprimarily computerized tomography scan or endoscopic retro-rade cholangiopancreatography [ERCP]) or histology.
The present study included CP patients (n � 150) in the NAPS2ohort enrolled from the University of Pittsburgh Medical CenterUPMC). Of these, 4 patients were excluded owing to missing ornsufficient information relevant to this study (n � 2), diagnosis ofntraductal papillary mucinous neoplasm (n � 1), or a change iniagnosis to RAP (n � 1), thereby resulting in a final studyopulation of 146 patients. All patients provided informed con-ent for review of their records; the study was approved by theniversity of Pittsburgh Institutional Review Board.
Data CollectionWe reviewed study data collected for all patients at the
time of NAPS2 enrollment as well as medical records bothbefore enrollment and during the follow-up period (ie, untilJanuary 1, 2011). Data in this study therefore are presentedrelating to the patients’ presentation at the time of initialevaluation at UPMC and relevant to the timing and follow-upperiod after ET and/or surgery. Data were recorded regardingchronic (not associated with episodes of acute pancreatitis) paincharacteristics (intermittent, constant), use and type of painmedication (non-narcotic, narcotic), and frequency of pain (in-termittent, daily), and presence of RAP, jaundice/cholestasis,diabetes, and steatorrhea. Baseline pancreatic and biliary find-ings, including pancreatic morphology, pancreatic and/or bili-ary ductal dilation, strictures, stones, leak, pseudocysts, anddivisum on abdominal imaging studies (computerized tomog-raphy scan, magnetic resonance imaging, ultrasound, andERCP) were recorded for all patients. ERCP reports were re-viewed for the number and indications of procedures, diagnos-tic findings, therapeutic interventions, complications, and du-ration of therapy. Surgical reports were reviewed for proceduretype, surgical findings, and technical success. Endoscopic orsurgical treatment before evaluation at UPMC also was re-corded.
Patient ClassificationWe classified patients according to pancreatic morphol-
ogy to evaluate technical and clinical success in homogenousgroups.6 Categories were based on the presence of dominant PDmorphology as follows: (1) strictures in the PD in head/body,(2) stones in the PD in head/body, (3) both strictures andstones, and (4) complex pathology (strictures, stones) but dila-tion in the PD body/tail. Patients who did not have thesefindings were categorized as follows: (5) isolated biliary stric-ture, (6) isolated pancreatic divisum, (7) isolated papillary ste-nosis, or (8) isolated leak/pseudocyst. For each patient we alsonoted the treatment modality: endoscopic, surgical, or medical(Figure 1). Indications for ET included symptoms related to CP,failed medical therapy, and changes on imaging amenable toendoscopic treatment (ie, stones, strictures, PD dilation, and soforth).
Bridge PatientsA subset of patients for whom the gastroenterologist
and gastrointestinal surgeon believed surgery was the optimalapproach was classified as bridge to surgery patients. Their
pancreatic morphology typically showed an inflammatory mass
or extensive calcifications in the pancreatic head. ET was per-formed as a temporary measure to delay the surgery untilresolution of inflammatory changes, to assess response to duc-tal decompression as a predictor of response to surgery, or inpatients who refused surgery in favor of ET. Clinical success ofET was not assessed in these patients because of the shortduration of treatment and short follow-up period between ETand surgery.
Technical Outcomes and Complications of ETAll ERCPs at UPMC were performed by 1 of 4 expert
therapeutic endoscopists. The technical success of ET (Table 1)was determined for each morphologic finding requiring therapyand was divided into 3 categories: complete, partial, failure. Ifmore than one morphologic feature was present (eg, stricturesand stones), complete success required that all features beresolved. ET was considered complete if no further ERCP ses-sions were performed after the initial treatment series, and nostents were left in situ. Otherwise, ET was considered to beongoing at the time of last follow-up evaluation. A temporarystent refers to stents without internal fixation, placed to reducethe risk of post-ERCP pancreatitis. Migration was confirmed onabdominal radiograph at 1 week; otherwise, stents were re-moved endoscopically.
Post-ERCP pancreatitis was defined as new or worsenedabdominal pain with an amylase and/or lipase increase 3 or
Figure 1. Schematic representation of patient stratification and dataanalysis.
more times the upper limit of normal more than 24 hours after
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July 2012 ENDOSCOPIC THERAPY IN CHRONIC PANCREATITIS 797
procedure. Cholangitis was defined as a temperature of 38°C orhigher for 24 to 48 hours after the procedure believed to be ofbiliary origin. Bleeding was defined as clinical evidence of gas-trointestinal blood loss after ET irrespective of transfusionrequirement or further procedures to achieve hemostasis. Hos-pitalization for 24-hour observation without any other compli-cations after ERCP also was recorded as a complication.
Clinical Outcomes of Endoscopic Therapy andSurgeryFollow-up data were collected through January 1, 2011.
The presence of symptoms (pain, RAP, jaundice/cholestasis)was recorded for every clinical contact during follow-up evalu-ation. Clinical success of ET and surgery (Table 1) were dividedinto 3 categories: complete, partial, and failure. If more thanone symptom was present (eg, chronic pain and RAP), completesuccess required fulfilling criteria for all symptoms. The needfor surgery at any time during the follow-up period was con-sidered clinical failure of ET.
Medical ManagementPatients who underwent no ET or surgery after their
diagnosis of CP were considered to be managed medically.Medical management included analgesic medications (non-nar-cotic, narcotic), pancreatic enzyme supplementation, counsel-ing for abstinence from alcohol and tobacco, and dietary rec-ommendations. Follow-up symptoms were classified as follows:(1) remained asymptomatic (never developed symptoms), (2)improved (discontinued or remained off narcotics with im-proved pain frequency), and (3) ongoing or worsened (contin-ued or increased pain and narcotic use).
Statistical MethodsDescriptive statistics are presented as proportions for
categoric data and as mean � standard deviation or median
Table 1. Criteria Used for Technical and Clinical Success andand Presenting Symptoms
Complete success
Technical outcomePD stricture Successful dilation, with the stricture wai
and/or successful stent placement acrPD stone Complete removal of intraductal stones w
remainingPD leak Resolution of the leak on pancreatogram
extravasation of contrast or recurrent flBiliary stricture Successful dilation, with the stricture wai
and/or successful stent placement acrDivisum Successful stent placement in the dorsal
minor papillotomyPapillary stenosis Successful dilation, stent placement acro
and/or pancreatic sphincterotomyClinical outcome
Pain Reduction in frequency of pain (not daily)discontinuation of narcotic medications
RAP No further episodes of acute pancreatitisJaundice/cholestasis Resolution of jaundice or cholestasis with
percutaneous biliary drainage or surger
NOTE. Partial success was an intermediate category between comple
(interquartile range) as applicable. Bivariate comparisons were
performed using the chi-square test or the Fisher exact test forcategoric data and the Student t test or the Mann–Whitney Utest for continuous data depending on the data distribution. AP value of less than .05 was considered significant.
ResultsPatient CohortOverall, age at initial diagnosis of CP was 44 � 18 years,
52% were male and 89% were Caucasian. The etiology wasalcohol in 60 (40%), idiopathic in 47 (32%), genetic in 17 (12%),hypertriglyceridemia in 8 (5%), divisum in 8 (5%), sphincter ofOddi dysfunction in 3 (2%), autoimmune in 2 (1%), and biliaryin 1 (1%) patient. Symptoms at the time of initial evaluation atUPMC included abdominal pain (93 patients; 64%), RAP (71patients; 48%), jaundice/cholestasis (17 patients; 12%), diabetes(13 patients; 9%), and steatorrhea (35 patients; 24%). Abdominalpain was characterized as constant in 50 of 93 (54%) patients.Analgesic medications were used by 80 of 93 (86%) patients:non-narcotic in 7 of 80 (9%), intermittent narcotic in 30 of 80(38%), and daily narcotic in 43 of 80 (54%).
Treatment GroupsThe distribution of patients into groups and follow-up
evaluation based on treatment type are shown in Figure 1. Ofthe 146 CP patients, 13 (9%) had undergone pancreatic surgerybefore evaluation at UPMC, 48 (33%) were managed medically,and 85 (58%) underwent ET (14 of 85 [16%] at outside facilities,17 of 85 [20%] both at outside facilities and at UPMC, and 54of 85 [64%] only at UPMC). Compared with patients who weremanaged medically, patients who underwent ET were signifi-cantly younger, more likely to have any pain or constant pain,required more narcotics, and were more likely to have jaundice/
lure of Endoscopic Therapy Based on Anatomic Findings
Failure
appearing,tricture
Dilation is without appreciable effect, and/or a stentcould not be placed across stricture
o stones Stone burden cannot be reduced appreciably
noollection
Ongoing leak refractory to ET and/or requiringsurgical treatment
appearing,tricture
Dilation is without appreciable effect, and/or stentcould not be placed across stricture
and/or Inability to place a stent in the dorsal duct orperform a minor papillotomy
e papilla, Inability to place a stent across the papilla orperform a pancreatic sphincterotomy
No reduction in the frequency of pain and/orongoing use of daily narcotics
ET No change in the frequency of episodes of RAPeed for No change in jaundice/cholestasis and/or need for
PTC or surgery
ccess and failure.
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and
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798 CLARKE ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 10, No. 7
Imaging Findings and Morphologic GroupsImaging findings on cross-sectional studies and/or
ERCP of the ET and medically managed groups are presented inTable 2. Overall, frequent findings included PD dilation, PDstones, and PD strictures, which were present in 71%, 38%, and32% of patients, respectively. Less common findings includedpapillary stenosis (11%), pseudocysts (22%), PD leak (6%), andcommon bile duct dilation (17%). Compared with patientsmanaged medically, patients who underwent ET were morelikely to have PD dilation, PD strictures, pancreas divisum, PDleak, and common bile duct stricture.
Patients who underwent ET were categorized based on mor-phologic findings into the following groups: PD strictures, 18patients (25%); PD stones, 15 patients (21%); PD stones plusstrictures, 14 patients (20%); complex morphology, 5 patients(7%); isolated pancreas divisum, 4 patients (6%); isolated papil-lary stenosis, 7 patients (10%); isolated PD leak/pseudocyst, 4
Table 2. Initial Clinical Data and Anatomic Findings inChronic Pancreatitis Patients Treated Medically orWith Endoscopic Therapy
Endoscopictherapy
(n � 85)
Medicalmanagement
(n � 48) P value
DemographicsAge at diagnosis, ya 41 (31–53) 53 (32–66) .04Male sex, n (%) 43 (51) 26 (54) .69White race, n (%) 73 (86) 44 (92) .33Smoker, n (%) 59 (69) 28 (58) .20
OD, sphincter of Oddi dysfunction.aMedian (interquartile range) shown.bData were collected at the time of the initial evaluation at UPMC.
patients (6%); and isolated biliary stricture, 4 patients (6%).
Endoscopic TherapyOf the 85 patients who underwent ET, 14 had ET
performed only at outside institutions. Because of the lack ofprocedure details in these patients, subsequent analysis is pre-sented only for patients who underwent ET at UPMC (Table 3).In these 71 patients, ERCP was performed with therapeuticintent in 63 (89%) and as a bridge to surgery in 8 (11%) patients.A total of 247 ERCP sessions were performed (median, 2 ses-sions; range, 1–17 sessions). In 13 (18%) patients with pancre-atic divisum, treatment was performed through the minor pa-pilla. Overall, complete or partial technical success was achievedin 60 of 71 (85%) patients.
There were several notable differences in ET among themorphologic groups. Patients with isolated PD stones under-went fewer ERCP sessions (mean, 2.1 sessions) than patientswith isolated strictures (mean, 5.0 sessions; P � .024), strictures
lus stones (mean, 4.1 sessions; P � .066), or complex mor-hology (mean, 4.8 sessions; P � .001). The mean duration of
therapy also was shorter for the PD stone group (9 mo) com-pared with the stricture group (39 mo; P � .023) and theomplex group (44 mo; P � .049). More PD stents were placedn the stone plus stricture group (100%) compared with thesolated stone group (67%; P � .037) and the isolated strictureroup (72%; P � .032). The presence of concurrent biliary
able 3. Details of Endoscopic Therapy in ChronicPancreatitis Patients
Patients with ET atUPMC (n � 71)
RCP, na 2 (1–4)uration of therapy, moa 4 (�1 to 29)ridge to surgery, n (%) 8 (11)ancreatic therapyPancreatic sphincterotomy, n (%) 43 (61)Dilation performed, n (%) 24 (34)
Number of dilationsa 2 (1–2.75)Dilation size, mma 4 (4–6)
Stone extraction, n (%) 26 (37)ESWL performed, n (%) 6 (8)PD stent placement, n (%) 53 (75)Temporary stent, n (%) 28 (39)
Number of stentsa 1 (1–1.25)Therapeutic stent, n (%) 44 (62)
Number of stentsa 2 (1–3)Number of sittingsa 2 (1.3)Stent length, cma 7 (7–9)Stent size, Fa 7 (7–7)
iliary therapyBiliary sphincterotomy, n (%) 31 (44)Dilation, n (%) 7 (10)Stent placement, n (%) 19 (27)
Number of stentsa 2 (1–4)Number of sittingsa 2 (1–4)Stent length, cma 7 (7–9)Stent size, Fa 10 (10–10)
Transgastric pseudocyst drainage, n (%) 3 (4)EUS/ERCP/both 1/1/1
July 2012 ENDOSCOPIC THERAPY IN CHRONIC PANCREATITIS 799
strictures and the rate of technical success were similar amongall morphologic groups.
Success and Complications of EndoscopicTherapyOf the 71 patients who underwent ET at UPMC, com-
plete follow-up data were available for 63 (89%) patients. Fourpatients were lost to follow-up evaluation, 3 patients were stillundergoing ET at the last follow-up evaluation, and 1 patientwas diagnosed with pancreatic cancer during ET. The meanduration of follow-up evaluation after completion of ET was 4.8 �3.0 years (range, 0.5–13 y). Complete or partial clinical successwas seen in 28 of 55 (51%) patients who completed ET with atherapeutic intent (Table 4). Excluding patients who also un-derwent ET at outside institutions before enrollment, clinicalsuccess of ET performed only at UPMC was seen in 26 of 45(58%) patients. Patients who responded to ET were more likelyto be older at the start of ET (47 vs 40 y; P � .10), have lessonstant pain (21% vs 52%; P � .031), require less dailyarcotics (14% vs 56%; P � .001), and have a shorter durationetween diagnosis of CP and start of ET (median, 4 vs 40 mo;� .017) (Table 5). There was no significant difference in
clinical success between the morphologic groups (data notshown). Among the 14 patients who underwent biliary stent-ing and had follow-up data, resolution of biliary stricturewas achieved in 9 of 14 (64%).
The overall incidence of complications related to ERCP was12% (29 of 247 sessions). Of these, 17 (59%) were hospitaliza-tions for observation alone. Specific complications includedpost-ERCP pancreatitis in 4% (9 of 247) and cholangitis in 1%
able 4. Complications and Technical and Clinical Successof Endoscopic Therapy and Surgery in 71 ChronicPancreatitis Patients Who Underwent EndoscopicTherapy at UPMC
n (%)
Complications of ET (n � 247 ERCPs)Total including all hospitalizations 29 (12)Total minus hospitalizations for observation 12 (5)Pancreatitis 9 (4)Infection 3 (1)
Technical success of ET (n � 70 completed ET)Complete 54 (77)Partial 6 (9)Failure 10 (14)
Clinical success of ET (n � 55 patients)a
Complete 23/55 (42)Partial 5 (9)Failure 27 (49)
Clinical success of surgeryTherapeutic ET groupb 17/60 (23)
aFifty-five of 71 patients completed ET with therapeutic intent and hadfollow-up data.
(bSixteen of 17 patients completed surgery and had follow-up data.
(3 of 247). There was no ERCP-related bleeding, perforation, ordeath. There was no significant difference in complication ratesbetween the morphologic groups or the bridge/therapeutic ETgroups (data not shown).
SurgeryOf the 132 patients with follow-up data, 44 (33%) pa-
tients underwent surgery (Figure 1). Among patients undergo-ing ET at UPMC, 25 of 71 (35%) required surgery. The rate ofsurgery among patients undergoing ET with therapeutic intent(ie, owing to clinical failure of ET) was 31% (17 of 55). All 8(100%) patients in the bridge to surgery group underwent sur-gery. Patients with isolated strictures were less likely to undergosurgery than patients with isolated stones (20% vs 62%; P �.025), stones plus strictures (20% vs 54%; P � .062), and com-plex morphology (20% vs 60%; P � .091), despite a similarclinical failure rate of ET. The mean time from completion ofET to surgery was 7 months (range, 0 – 68 mo).
Surgical procedures included Whipple (10), Frey (6), Puestow(2), Beger (1), Duval (1), total pancreatectomy with auto-isletcell transplant (1), distal pancreatectomy (1), and other (3).Technical success of surgery was observed in 24 of 25 (96%)patients. One patient was diagnosed with pancreatic cancerduring surgery. The mean duration of follow-up evaluationafter surgery was 4.3 � 3.4 years (range, 1–13 y). Complete orpartial clinical success with surgery was seen in 12 of 24 (50%)patients. There was no significant difference in response tosurgery between the morphologic groups (data not shown). Nofactors were identified as significantly associated with clinicalsuccess of surgery, although there was a trend toward responsefor patients with a short duration of disease (54 vs 87 mo; P �.19), and in the bridge to surgery group compared with thetherapeutic ET group (63% vs 44%; P � .40).
Medical ManagementOverall, 48 of 146 (33%) patients were managed medi-
cally. One-quarter of patients (12 of 48) were asymptomatic atthe time of initial presentation and all remained asymptomaticduring the follow-up period. There were no significant morpho-logic differences between symptomatic and asymptomatic pa-tients (data not shown). The mean duration from time of CPdiagnosis to last follow-up evaluation in medically managedpatients was 5.7 � 4.1 years (range, 0.3–19 y). Of the 36 of 48
Table 5. Factors Associated With Long-term ClinicalResponse to Endoscopic Therapy in ChronicPancreatitis Patients
Responseto ET
(n � 28)
No responseto ET
(n � 27) P value
Age at diagnosis, ya 47 � 19 40 � 13 .10onstant pain, n (%) 6 (21) 14 (52) .031aily narcotics, n (%) 4 (14) 15 (56) .001uration of disease, mob 4 (1–12) 40 (1–60) .017
OTE. There was no difference in response based on etiology ororphologic groups.
aMean � standard deviation.bMedian (interquartile range).
75%) patients who had symptomatic disease, 11 (31%) had
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800 CLARKE ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 10, No. 7
significant improvement in symptoms, 19 (53%) had no changeor an increase in symptoms, and 6 (17%) were lost to follow-upevaluation. There were no significant differences in morphologybetween patients who improved and those who remained symp-tomatic (data not shown). Four of 19 (21%) persistently symp-tomatic patients underwent surgery during the follow-up pe-riod, with clinical success of surgery comparable with that ofthe ET group.
Endocrine and Exocrine DysfunctionAmong the 132 patients with complete follow-up data,
19 (14%) developed new diabetes and 8 (6%) developed newsteatorrhea during the follow-up period. There was no signifi-cant difference in the development of diabetes and steatorrheabetween patients based on the type of treatment received (datanot shown).
MortalityThe 10 (7%) patients who died during the follow-up
period were distributed equally in the ET and medically man-aged groups. The cause of death included pancreatic cancer (4patients), other malignancy (2 patients), infection (2 patients),GI bleed (1 patient), and spontaneous ulcer perforation (1patient). The mean duration between diagnosis of CP and deathwas 4.7 years (range, 0.5–15 y).
DiscussionWe found that patients undergoing ET were more
symptomatic and had more complex morphology than patientswho were managed medically. ET was safe, technically success-ful in most patients, and achieved long-term clinical success inmore than half of patients. Long-term clinical success also wasachieved in half of all patients who underwent surgery afterfailed ET or in whom ET was used as a bridge to surgery.
CP patients comprise a heterogeneous population with avariety of symptoms, morphologic features, and disease-relatedcomplications. Nearly 40% of patients who underwent ET inour study had more than one symptom (pain, RAP, jaundice),and all but one patient (biliary stricture alone) who underwentET presented with abdominal pain as a component of theirdisease. Similarly, nearly 40% of patients who underwent EThad an additional morphologic finding outside the PD (biliarystricture, pseudocyst). These findings highlight the presence ofclinical symptoms and morphologic features that can guideselection of patients for ET and/or surgery.
Morphologic features may affect the technical and clinicalsuccess of ET in CP patients. Because previous studies haveshown a higher rate of clinical success of ET in patients withPD strictures over stones,6 we took morphology into account
hen stratifying patients into homogenous groups beforevaluating the efficacy of ET. Although we noted differencesn terms of the number of ERCPs and stents placed (highern patients with strictures vs without strictures), technicalnd clinical success rates of ET and surgery were similarmong morphologic groups. Our results suggest that specificaseline morphologic characteristics may not predict long-erm clinical outcomes of ET.
Rather than focusing on short-term clinical efficacy, whichay diminish over time, we assessed the long-term clinical
utcomes of ET. Clinical success in our study (51%–58%) was
omewhat lower than in other large series (54%–94%) withedium- to long-term follow-up evaluation.6 –17 A lower re-
sponse rate in our study may be owing to the long duration offollow-up evaluation, inclusion of patients with multiple mor-phologic features, and differences in assessing outcome of ET(eg, narcotic discontinuation in our study vs hospitalizations,pain scores, and so forth). As in previous studies, we found thata shorter duration of disease was associated with a higherclinical success rate.7,8,12,22,23 This suggests that a degree ofrreversibility develops as CP progresses, and may indicate a roleor endoscopic or surgical intervention early in disease course.n contrast to prior studies, we found that patients with lessevere symptoms (lack of constant pain or use of daily narcot-cs) were more likely to achieve clinical success after ET. Theresence of constant pain may be an indicator of more ad-anced disease, different pain mechanisms, or visceral hyperal-esia, thereby affecting the success of ET. Daily narcotic useay confer a degree of narcotic dependence that impedes dis-
ontinuation of narcotics after ET independent of improve-ent in pain. In fact, prior CP surgical series have shown that
atients on opioids preoperatively are more likely to continuehem postoperatively despite improvement in pain.23 Failure of
endoscopic ductal decompression suggests a pathogenesis ofpain other than intraductal hypertension.
In our cohort, 44 of 146 (30%) patients overall and 27 of 85(32%) patients after ET underwent surgery. Clinical success aftersurgery was seen in 50%. The rate and outcomes of surgery inprior studies have been highly variable. Surgery rates in CPpatients were much higher in earlier studies when ET was notperformed routinely (56%–72%).23,34 Most studies either as-essed effectiveness of surgery as initial treatment (ie, withoutrior attempts at ET), or did not provide details regarding ETefore surgery. The clinical success rates in these series haveanged from 53% to 95%,21–32 although recurrence of pain overery long follow-up periods (�10 y) has been reported to be asigh as 56% to 65%.34 –36
Clinical success after surgery depends on whether surgery isperformed in naive patients or in those who have failed ET. Aunique aspect of our study was the evaluation of surgicaloutcomes after failed ET. This represents a negative selection ofpatients, which may explain our somewhat lower surgical suc-cess rate compared with previous studies. Our approach, how-ever, is consistent with the current guidelines, which suggest ETas an initial approach, reserving surgery for cases of failure orrecurrence of symptoms.37 Interestingly, the overall clinical suc-ess rate of ET plus surgery was 66%, which is similar to surgicaleries. Three other studies reported detailed descriptions of ETnd subsequent surgery, with clinical success in 63% to 79% ofatients.6,9,15 Two of these studies had small numbers of pa-
tients (8 and 12 patients),9,15 whereas the third did not reportollow-up duration after surgery.6
Our study differed from previous reports in stratifying pa-tients according to whether ET was performed with a therapeu-tic intent or as a bridge to surgery. The bridge group comprisedpatients for whom surgery was believed to be the ideal treat-ment. ET was performed as a temporary measure to permitresolution of inflammatory changes in the pancreatic/peripan-creatic area, to accommodate the patient’s request for an initialattempt at ET rather than surgery, or to assess whether surgerywould be beneficial (eg, decompression of PD before consider-
ation of a Puestow surgery). Not surprisingly, surgery in these
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1
1
1
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July 2012 ENDOSCOPIC THERAPY IN CHRONIC PANCREATITIS 801
patients did show a trend toward better success than those inthe therapeutic ET group (63% vs 44%). The decision to performET as a bridge to surgery should be made in collaborationbetween the gastroenterologist, therapeutic endoscopist, andsurgeon to individualize treatment approach.
Another unique aspect of our study was the inclusion of amedically managed arm. This reflects the natural history of CPin patients treated at a referral center. Although most medicallymanaged patients (75%) were symptomatic at the time of pre-sentation, their symptoms were milder and their morphologywas less complex when compared with patients who underwentET, justifying a conservative approach to treatment. Interest-ingly, spontaneous improvement was seen in 11 (31%) patients,which is somewhat lower than prior studies describing thenatural history of CP (35%–70%).34,36,38 This difference may beexplained by the longer duration of follow-up evaluation (�10y) in other natural history studies.
Limitations of our study included a retrospective analysis ata single tertiary academic center. Such retrospective studies canoverestimate clinical success and underestimate complications.Our cohort likely suffered from referral bias because patientswho have more symptomatic or complex disease are more likelyto be referred to a tertiary center. Follow-up data were availablefor 89% of patients, which provided a good, but not compre-hensive, degree of data completeness. We did not assess short-term effectiveness of ET because effectiveness is thought todiminish over time, making long-term results a more usefulassessment of overall effectiveness. Finally, the cohort presentedhere does not include CP patients treated at UPMC who werenot enrolled in the NAPS2 study.
In conclusion, we evaluated and compared the long-termoutcomes of ET with those of surgery and medical managementin a large cohort of CP patients treated at a tertiary academiccenter. In expert hands, ET was safe and achieved long-termclinical success in more than half of patients. Among patientswho failed ET, surgery achieved clinical success in half of theremaining patients. Overall, clinical success of ET and surgerywas seen in 63%. We propose a stepwise approach for managingCP, starting with medical management. Patients who are symp-tomatic and have appropriate morphologic features should beconsidered for ET early in the disease course. A subset ofpatients will require surgical intervention, with or without ETas a bridge to surgery, based on an individualized assessment ofrisk and benefit. An interdisciplinary approach is critical toproviding effective, safe, and lasting palliation of symptoms.
Supplementary MaterialNote: To access the supplementary material accompa-
nying this article, visit the online version of Clinical Gastroenter-ology and Hepatology at www.cghjournal.org.
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Reprint requestsAddress requests for reprints to: Dhiraj Yadav, MD, MPH, Division of
Gastroenterology and Hepatology, Department of Medicine, Universityof Pittsburgh Medical Center, 200 Lothrop Street, M2, C-Wing, Pitts-burgh, Pennsylvania 15213. e-mail: [email protected]; fax: (412)383-8992.
AcknowledgmentsThe authors thank Michelle L. Kienholz, Department of Medicine,
University of Pittsburgh, for critical review and editorial assistance.This study was presented as a Poster at Digestive Disorders Week,
May 2011, Chicago, Illinois.
Conflicts of interestThe authors disclose no conflicts.
FundingThis research was supported by National Institutes of Health
(National Institute of Digestive and Diabetes and Kidney Disease[NIDDK]) (DK061451 to D.C.W.), the National Pancreas Foundation(D.C.W.), Robert and Vicki Hall, and Andrew and Michelle Aloe. DrYadav is supported in part by the National Institutes of Health
