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Chronic pancreatitis
Novel concepts in diagnostics and treatment
Issa, Y.
Publication date
2017
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Issa, Y. (2017). Chronic pancreatitis: Novel concepts in diagnostics and treatment.
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CHAPTER 5
DUTCH CHRONIC PANCREATITIS REGISTRY (CARE):
DESIGN AND RATIONALE OF A NATIONWIDE PROSPECTIVE
EVALUATION AND FOLLOW-UP
U.A. Ali, Y. Issa, H. van Goor, C.H. van Eijck, V.B Nieuwenhuijs, Y.C. Keulemans, P. Fockens, O.R. Busch, J.P. Drenth, C.H. Dejong, H.M. van Dullemen, J.E. van Hooft, P.D. Siersema, B.W.M. Spanier, J.W. Poley, A.C. Poen, R. Timmer, T. Seerden, A.C. Tan, W.J. Thijs, B.J. Witteman, T.E. Romkens, A.J. Roeterdink, H.G. Gooszen, H.C. van Santvoort, M.J. Bruno, M.A. Boermeester; Dutch Pancreatitis Study Group.
ABSTRACT
Background
Chronic pancreatitis is a complex disease with many unanswered questions regarding the natural history and therapy. Prospective longitudinal studies with long-term follow-up are warranted.
Methods
The Dutch Chronic Pancreatitis Registry (CARE) is a nationwide registry aimed at prospective evaluation and follow-up of patients with chronic pancreatitis. All patients with (suspected) chronic or recurrent pancreatitis are eligible for CARE. Patients are followed-up by yearly questionnaires and review of medical records. Study outcomes are pain, disease complications, quality of life, and pancreatic function. The target sample size was set at 500 for the first year and 1000 patients within 3 years.
Results
A total of 1218 patients were included from February 2010 until June 2013 by 76 participating surgeons and gastroenterologist from 33 hospitals. Participation rate was 90% of eligible patients. Eight academic centers included 761 (62%) patients, while 25 community hospitals included 457 (38%). Patient centered outcomes were assessed by yearly questionnaires, which had a response rate of 85 and 82% for year 1 and 2, respectively. The median age of patients was 58 years, 814 (67%) were male, and 38% had symptoms for less than 5 years.
Discussion
The CARE registry has successfully recruited over 1200 patients with chronic and recurrent pancreatitis in about 3 years. The defined inclusion criteria ensure patients are included at an early disease stage. Participation and compliance rates are high. CARE offers a unique opportunity with sufficient power to investigate many clinical questions regarding natural course, complications, and efficacy and timing of treatment strategies.
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INTRODUCTION
Chronic pancreatitis (CP) is a complex disease with several uncertainties regarding natural course, diagnosis and outcome of treatments [1-4]. Few long-term prospective cohort studies have been performed to study these issues [5-8]. Most of these are single center cohort studies that have been conducted in time periods varying from one to three decades. Although these studies have been valuable in furthering our understanding of CP, certain results differed notably and have led to contradicting conclusions regarding issues such as types of pain patterns observed, ‘burn-out hypothesis’ and optimal timing of interventions [2]. In addition, acquiring a sufficient number of patients remains challenging due to the relatively low incidence of CP. It is, therefore, generally acknowledged that large prospective multi-center cooperative initiatives are warranted [9]. The Dutch Pancreatitis Study Group (DPSG) has been successful in conducting several multicenter research projects facilitated by the advantageous geographic and demographics properties of the Netherlands [10,11]. It is estimated that in the Netherlands there are approximately 300 to 800 new cases of CP every year [12,13]. With coverage of over 30 out of 100 hospitals in the Netherlands, including all eight Academic Centers, the DPSG has the potential of including large numbers of patients in a relatively short time. The Dutch Chronic Pancreatitis Registry (CARE), outlined here, has been designed to utilize this potential to prospectively evaluate and follow-up patients with CP on a national level.
PATIENTS AND METHODS
Design
National registration and prospective follow-up study.
Aims
• To evaluate the natural course of CP and describe the Dutch CP patient population.
• To study the influence of relevant clinical and morphological factors on the course and outcomes of the disease.
• To form a basis for future prospective observational and experimental studies.
Setting
This study is coordinated by the Dutch Pancreatitis Study Group, a cooperation of Dutch hospitals dedicated to the study of acute and chronic pancreatitis. CARE is open for all Dutch hospitals willing to participate. All 8 university medical centers in the Netherlands are participating in this study, as well as 25 community hospitals distributed all over the country, which is over a third of all Dutch hospitals. Gastroenterologists, surgeons and internists work together in recruiting and following patients.
Patient population
All adult patients with confirmed or high suspicion of CP or with recurrent acute pancreatitis (RAP) are eligible for inclusion in the CARE study. Due to the complexity of the diagnosis of CP, final confirmation of the diagnosis will be made at time of data analysis. Patients will be divided into three groups based on clinical and radiological criteria:
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• Patients with probable CP, according to the M-ANNHEIM criteria (Table 1) [14]. • Patients with definite CP, according to the M-ANNHEIM criteria (Table 1) [14]. • Patients with RAP (two or more documented attacks), with no imaging evidence for CP.
Table 1. Definite and probable chronic pancreatitis according to the M-ANNHEIM criteria
The diagnosis of chronic pancreatitis requires a typical clinical history of chronic pancreatitis (such as recurrent pancreatitis or abdominal pain), except for primary painless pancreatitis.
Definite chronic pancreatitis is established by one or more of the following additional criteria: 1. Pancreatic calcifications.
2. Moderate or marked ductal lesions (according to the Cambridge classification).
3. Marked and persistent exocrine insufficiency defined as pancreatic steatorrhea markedly reduced by enzyme supplementation.
4. Typical histology of an adequate histological specimen.
Probable chronic pancreatitis is established by one or more of the following additional criteria: 1. Mild ductal alterations (according to the Cambridge classification)
2. Recurrent or persistent pseudocysts
3. Pathological test of pancreatic exocrine function (such as fecal elastase-1 test, secretin test, secretin–pancreozymin test) 4. Endocrine insufficiency (i.e., abnormal glucose tolerance test)
Registration of patients
Eligible patients are asked to participate by their treating physicians. Patients are requested permission to send their personal information to the study datacenter. Study personnel then approach the patient and explain the study in further detail. A study package containing a patient information letter, a written informed consent form and study questionnaires is sent to consenting patients. Patients are enrolled in the study after they have returned the signed written informed consent.
Data collection and follow-up
After inclusion, patients are followed regularly by means of yearly questionnaires and regular review of medical records. Our aim is to follow-up patients over a prolonged period of time of at least 5 to 10 years. Collected data focuses on potentially relevant determinants of the disease as well as patient centered outcomes, such as pain, pancreatic function and quality of life. Below we present a detailed description of the collected data:
Study questionnaires
General questionnaire:
These include questions regarding social economic status, weight, height, smoking (duration and quantity), alcohol use (duration, quantity and history of past periods with excessive drinking), time of onset of pain symptoms, time of first referral to specialist for pain symptoms, pain location, pain pattern (continuous vs. intermittent), presence of other symptoms (jaundice, diarrhea, steatorrhea, dietary problems), medication, hospitalization and interventions for pancreatic problems.
Validated pain questionnaires:
• Izbicki pain questionnaire [15]: measures nociceptive pain and includes a pain visual analogue score (VAS).
• PainDETECT questionnaire [16]: is used to screen for presence of neuropathic pain.
• Pain Coping and Cognition List (PCCL) [17]: measures the coping mechanisms of patients to pain (administered once every 5 years).
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Validated quality of life questionnaires:• Short-form 36 (SF-36)[18].
• EuroQoL EQ-5D questionnaires [19].
• EORCT QLQ-C30 with the PAN-28 module [20]: this is a relatively new quality of life questionnaire validated specifically for CP (administered once every 5 years).
Regular review of medical records
Study personnel will review medical records at enrollment and regularly thereafter (at least once every three years) to collect the following data:
• Relevant additional investigations:
• Imaging: reports of all ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), endoscopic retrograde cholangiopancreaticography (ERCP) and endoscopic ultrasound (EUS) investigations of the pancreas. All imaging modalities specified in the M-ANNHEIM classification are used to establish the diagnosis of CP (i.e. US, CT, MRI, EUS and ERCP). Since CARE is an observational study, the study protocol does not dictate a certain modality to be used. However, most common practice for diagnosis and follow-up of CP in the Netherlands is the use of high quality CTs using a pancreas protocol. When this is inconclusive or more detailed information about duct abnormalities are needed, MRCP or EUS are used depending on availability and expertise. ERCPs are most commonly used when there is a potential for intervention, since pure diagnostic ERCPs are often avoided.
• Pancreatic function: any test for endocrine or exocrine pancreatic function. Currently in our setting the most used test is the fecal elastase-1 level measurement, followed by the quantitative measurement of fecal fat over 72 hours.
• Hospitalization and interventions:
• Referral and discharge letters for hospitalizations
• Reports of any relevant endoscopic or surgical intervention
Study size, accrual and drop-out rates
The target number of patients was 500 for the first year and 1000 patients within 3 years. Based on an incidence rate of about 500 new patients per year, and our accrual area (about 35% of hospitals in the Netherlands) we expect a subsequent patient accrual rate of around 150 new patients per year. Drop-out rates were expected to increase with longer follow-up periods due to multiple reasons such as death, diagnosis proven not to be CP and patient’s unwillingness or inability to participate for a prolonged period of time.
Ethics and informed consent
This project has been set up in accordance with the principles of the Declaration of Helsinki and according to the laws governing human research in the Netherlands (Wet Medisch-wetenschappelijk Onderzoek met mensen - WMO) and the guidelines of the Dutch Central Commission for Human Bound Research (Centrale Comissie Mensgebonden Onderzoek - CCMO). This study has been reviewed by the medical ethical committee of the University Medical Center Utrecht, and was given exempt status due to its descriptive nature (ID: AvG/rc/10/05699, 17 March 2010). All patients provide written informed consent before participation. Also, patients are asked explicitly for permission to obtain relevant data from medical records.
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Infrastructure and privacy
The CARE infrastructure is housed in a dedicated Datacenter of the Department of Surgery of the Academic Medical Center Amsterdam. Study data is not allowed to leave the Datacenter, and only approved study personnel have access. The study personnel consist of two dedicated research nurses with extensive experience in pancreatitis research, a study coordinator who supervises daily activities and the principal investigator. The study data are stored in a secure local (not accessible online), password-protected database. The database for CARE has been developed by the Clinical Research Unit (CRU) of the Academic Medical Center Amsterdam.
Expertpanel
As part of CARE, the Dutch Pancreatitis Study Group has launched a national Expertpanel for CP. This panel consists of 16 national experts from all relevant specialties (gastroenterologists, surgeons and radiologists). The Expertpanel functions as a dedicated knowledge and expertise body to which physicians can turn for advice about complex CP patients encountered in their clinical practices. The Expertpanel offers its advise to all physicians and CP patients in the Netherlands regardless of participation in CARE.
Research questions
By registering and prospectively following CP patients, CARE offers an opportunity to answer many relevant questions. Study questions can be suggested by all participating physicians, and are discussed within the protocol committee. Study protocol will be designed for each substudy and subsequently carried-out within CARE. Most data pertaining to these research questions are already part of the data set collected within CARE. When needed, additional data can be collected during from medical records.
Currently two research questions have been proposed and accepted for further analysis within CARE. The first question will study the pain patterns (e.g. type A and B pain) of patients with CP during different stages of their disease. The aim is to describe the different pain patterns presented by patients, study whether and how these patterns evolve over time, and examine the relation of these pain patterns with efficacy of endoscopic and surgical treatments. The second question will study the timing of endoscopic and surgical intervention in CP, and especially focus whether earlier endoscopic or surgical interventions during the course of the disease results in better outcomes in terms of pain relief and quality of life.
RESULTS
Inclusion of patients started in February 2010. Seventy-six specialists (17 surgeons and 59 gastroenterologists) from 33 hospitals are currently participating in this study. On 30 June 2013, a total of 1359 patients were referred by their physicians as potential candidates for the study. Of those, 1218 (90%) patients consented and were included in the CARE registry (Figure 1). Average inclusion rate for the duration of the study (41 months) was 30 patients per month. The inclusion rate was relatively constant during the study period at an average of 30, 32 and 29 patients per months for the first, second and third year, respectively. Inclusion of patients per participating hospital is illustrated in Figure 2. Eight academic centers included 761 (62%) patients, while 25 community hospitals included 457 (38%) patients.
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Figure 1. Inclusion chart in CARE from February 2010 until June 2013Figure 2. Inclusion in CARE per hospital as of June 2013.
Hospitals indicated by an asterix (*) are academic medical centers. Remaining hospitals are community hospitals. 1400 1200 1000 800 400 600 200 0
Feb-2010 2010May- 2010Aug- 2010Nov- 2011Feb- May-2011 2011Aug- 2011Nov- 2012Feb- May-2012 2012Aug- 2012Nov- 2013Feb- May-2013 Eligible pa ents Included pa ents Ra dbou dU MC * Is al a UM CG * MU MC * Am phi a UM CU * Ma r ni JB Z MS T CW Z ZG V St A nt on iu s Ca th ar in a Ri jns ta te Me an der MC M aas st ad OL VG Ge lr e Vi ec ur ie Ha ga LU MC * MC H Br on ov o ZG T Rd GG VU MC * Be rn ho ve n Or bi s MC Sp aar ne St Jan sd al MC V EM C* AM C* 300 250 200 150 100 50 0 Eligible paents Included paents
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Figure 3. Distribution of patients according to reported duration of onset of symptoms
Characteristics of patients are presented in Table 1. Median age is 58 (IQR 50 to 65) years, and 814 (67%) are male. Median duration of symptoms (from first referral to specialist for pancreatic symptoms to inclusion) is 6 years (IQR 3 to 12) (Figure 3). Median age at referral to a specialist for pancreatic symptoms is 48 years (IQR 40 to 57). About 38% of the patients included in CARE are in the first 5 years of disease onset. Many patients are current smokers (53%) or have smoked in the past (32%). About half of the patients have a history of alcohol consumption of >40 grams per day (53%). Diabetic mellitus was prevalent in 503 (41%) of patients. Approximately 40% of patients have had at least one endoscopic intervention for CP, while a third had undergone a surgical procedure for their disease.
Response rates to questionnaires were high. Of the 780 patients scheduled for the first year follow-up by February 2013, 660 (84.6%) returned their questionnaires. Of the 120 patients who did not return their questionnaires, 23 (19%) were deceased, 36 (30%) withdrew from the study and 61 (51%) indicated they would fill in the questionnaire but subsequently did not (some did return the second years questionnaires). Similarly, of the 429 patients scheduled from the second year follow-up questionnaire on February 2013, 350 (82%) returned their questionnaires. Of the 79 patients that did not return their questionnaires, 9 (11%) were deceased, 26 (33%) withdrew from the study and 44 (56%) indicated they would fill in the questionnaire but have not done so yet.
RATIONALE AND DISCUSSION
CARE is a registry in which patients with CP can be identified and prospectively evaluated in an organized and systematic manner. This task can be quite challenging due to limited number of patients and resources. Not surprisingly, well-powered prospective CP cohorts are scarce. The CARE project has now shown to be successful in registering and following over 1200 patients with suspected or established CP in just over 3 years. Most importantly, cooperation of physicians and compliance of patients are high.
500 450 400 350 300 250 200 150
<5 years 5-9 years 10-14 years 15-19 years ≥20years 100
50 0
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Recently, three cooperative studies on CP have been reported in literature, i.e. the North American Pancreatitis Study (NAPS)-2, and the Italian and Indian survey for CP studies [21-23]. The aims and designs of these studies are different from those in CARE. All studies are cross-sectional studies, which limits the type of questions that can be answered. The NAPS-2 was generally a well designed study. The only potential limitation, as discussed by the authors, was the inclusion of patients from secondary and tertiary specialized centers only, potentially limiting the generalisability of results. The Italian and Indian studies provided an overview of demographic and disease related characteristics of the Italian and Indian patients, respectively, but did not shed more light on natural history or outcome of treatments. In addition, a number of single-center prospective cohort studies does exist [7,8,24]. These are often comprehensive cohorts that are able to collect detailed data on included patients. Unfortunately, due to low incidence of CP it takes a significant amount of time and dedication to be able to accrue enough patients. Also, results from such cohorts can benefit from external validation, for which there is limited opportunity at this moment.
Prospectively following patients with CP over time has considerable advantages. First, it allows to study various aspects of the natural course including levels and patterns of pain over time, impact of pancreatic function on pain (‘burn-out’ hypothesis) and patients’ lives. It also permits to evaluate the efficacy and timing of current treatment strategies. It also can shed more light on development and treatment of CP associated complications such as pancreatic cysts, bile duct and gastric outlet obstruction, and cancer development. Current knowledge of many of these aspects have only slightly evolved since Ammann and Lankish published the results of their longitudinal cohort about 20 years ago [5,25]. Importantly, clinical practice has changed over time, including the application of newer imaging modalities and advances in endoscopic and surgical interventions. It is, therefore, important to evaluate these topics with current patient data.
Applying broad inclusion criteria in CARE has been a deliberate choice in order to include patients at an early stage in their disease. This early stage is associated with minimal abnormalities on imaging and is a relatively less well studied phase of CP. In addition, inclusion of patients with recurrent pancreatitis is of interest to study the progression from RAP to CP and how to potentially prevent this.
Inclusion of patients with suspected disease does carry certain drawbacks. It increases the load on available resources, since a proportion of these patients might not progress to CP. Therefore, criteria need to be formulated when further follow-up is no longer useful. In a separate study, we are currently analyzing risk factor for the progression from a first acute pancreatitis episode to CP in a large multi-center cohort. Results of that study will be helpful to define criteria when to stop follow-up. Another drawback is that some patients with minimal symptoms feel that their situation does not relate to the questions about pain, steatorrhea and feeding problems. Our experience is that patients are quite willing to fill in the questionnaires initially, but often need additional explanation and stimulation to complete questionnaires in subsequent years.
The observational nature of CARE might also be considered a limitation. While this design precludes answering certain research questions, mainly causation questions, it does provide important advantages, such as lower costs, the ability to apply wide inclusion criteria, having a lower threshold for patients and physicians to participate, and the ability to evaluate current practices without actively interfering with existing treatments. CARE can also facilitate the design and roll-out of future studies.
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Certain challenges do exist for the long-term continuation of the CARE study. First, resources are limited while workload rises with the increasing number of patients. Second, maintaining a high level of patient participation can be challenging. To address these challenges, adaptations in the methods of data collection in the future might be necessary. For example, after initial evaluation a switch from annual to biannual patients’ questionnaires will be considered to reduce workload. Since CP is a long-term disease, a scheme of biannual follow-up seems justifiable. Keeping patients involved and informed about the relevance of their contribution to CARE are means to maintain high compliance. Examples in this respect are regular (e)mail updates about CARE and disease related information, as well as organizing educational meetings for patients. The protocol committee is continuously discussing these items in order to ensure the continuity of CARE
.
CONCLUSION
The CARE registry has successfully recruited over 1200 patients with chronic pancreatitis in a study period of 3 years. Participation and compliance rates are high. For long-term continuation and follow-up, maintaining high patient involvement and resources are essential. CARE offers a unique repository with sufficient power to investigate many clinical questions regarding natural course, complications, and efficacy and timing of treatment strategies.
Acknowledgment: This study has been funded by an unrestricted grant from Abbott Pharmaceuticals
and by The Dutch Pancreas Patients’ Association (Alvleesklierverenigi ng). The CARE study is an investigator initiated study and the funding entities had no influence on the design of the study. Neither do they have any influence on implementation, data collection, interpretation of results or decision to publish.
Authors’ contributions
UAA, YI, AJR and MAB co-authored the writing of the manuscript. UAA, HvG, CHvE, VBN, YK, PF, ORB, JPD, CHD, HMvD, PDS, BWMS, JWP, AJR, HGG, MJB and MAB participated in the design of the study. All authors critically assessed the study design and/or included patients in the study, edited the manuscript and read and approved the final manuscript
Collaborators within the Dutch Pancreatitis Study Group (all in the Netherlands, alphabetical order by center):
Academic Medical Center, Amsterdam: M.G.H. Besselink, D.J. Gouma, U.H. Beuers, E.A. Rauws, M. van der Vlugt, R.B. Takkenberg, S. Balkema, F. te Braake, J.J. Kloek, B.C.F.M. Schutijser; Amphia Hospital, Breda: A.G. Bodelier, M.J. van Heerde, A.W.M. van Milligen de Wit; Bernhoven Hospital, Oss: W.A. de Boer, B.P.J. van Balkom; Canisius-Wilhelmina Hospital, Nijmegen: C. Rosman, E.M. Witteman, C.C.G. van Enckevort; Catharina Hospital, Eindhoven: N. Wlazlo, S. van Stiphout, G.W. Schouten, L.P. Gilissen, E.J. Schoon; Diakonessenhuis, Utrecht: A.H. Oberndorff-Klein Woolthuis , B. van Tuyl, A.M.C.J. Voorburg; Erasmus Medical Center, Rotterdam: D.L. Cahen, S. Darwish Murad, U.S. Wiersema, P. Didden, J.J. Kuiper, G.W. Bezemer, H. Braat, C. Postma; Gelderse Vallei Hospital, Ede: R. Meiland; Gelre Hospital, Apeldoorn: , J.M. Omloo, P. van Duijvendijk, G.W. Erkelens, J. Scherpenisse; Haaglanden Medical Center, Leidschendam: L.E. Perk; Haga Hospital, Den Haag: M.H.M.G. Houben; Isala Clinics, Zwolle: A. Alkhalaf , B.E. Schenk, J. Vecht, W.H. de Vos, M.A.C. Meijssen, D. Oude Hergelink, J. Vecht, M.C. Visschedijk; Jeroen Bosch Hospital, ‘s-Hertogenbosch: O.J. Bakker, I.P. van
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Munster, A.D. Schryver, R.C.H. Scheffer; Leiden University Medical Center, Leiden: M.H. Degeling, L. Welling, A.F. Schaapherder, A. Inderson; Maasstad Hospital, Rotterdam: E. van der Harst, E.E. Colpaert, S. Ganesh, M. Hadithi, F.J.G.M Kubben; Maastricht University Medical Center, Maastricht: R.M. van Dam, A. Masclee; Martini Hospital, Groningen: H. van der Heide; Meander Medical Center, Amersfoort: K. de Jong, M.A. Brink, W.L. Hazen, H. Akol, M.P. Schwartz; Medisch Spectrum Twente, Enschede: J.J. Kolkman, N.G. Venneman; OLVG, Amsterdam: M.F. Gerhards , J.M. Jansen, F.O. The, F. van den Hanenberg, A. van der Sluijs Veer; Orbis Medical Center, Sittard-Geleen: E.T.P Keulen; RadboudUMC, Nijmegen: A.A. van Esch, T.M. Bisseling, F.J.C. Cuperus, J.M. Kersten, E.J.M. van Geenen; Reinier de Graaf Group, Delft: J.J.G. Scheepers, J.T. Brouwer, R. Quispel, B.J. Veldt, D.F.G.M. Josemanders; Rijnstate Hospital, Arnhem: J.M. Vrolijk; Spaarne Hospital, Hoofddorp: M.T. Uiterwaal; St. Antonius Hospital, Nieuwegein: D. Boerma, B. Ramshorst, M.C.J.M Becx, W.J. Bos, H.S. de Vries , J. Tenthof van Noorden, N. van Lelyveld, B.L. Weusten; St. Elisabeth Hospital, Tilburg: J. Heisterkamp; St. Jansdal Hospital, Harderwijk: M. Willems; University Medical Center Groningen, Groningen: J.W. Haveman, I.M. Kerkhof, J.M.J. Geesing, E.A.M. Festen, K. Havenga, E. Kouw, H.S. Hofker; University Medical Center Utrecht, Utrecht: I.Q. Molenaar, F.P. Vleggaar; VieCurie Medical Center, Venlo: R.P.R. Adang; VU Medical Center , Amsterdam: C.J. Mulder.
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Table 2. Characteristics of patients in CARE
Characteristics (N=1218)
Age at inclusion years [median (IQR)] 58 (50 - 65)
Gender males (%) 814 (67%)
BMI [median (IQR)] 23.9 (21.4 - 26.6)
Duration of symptoms years [median (IQR)] 6.0 (3.0 - 12.0)
Age at referral to specialist for symptoms years [median (IQR)] 48 (40 - 57)
Smoking n (%) - Never 173 (14%) - Past smoker 390 (32%) - Current smoker 651 (53%) Alcohol consumption n (%) - Never 160 (13%) - Past drinker 657 (54%) - Current drinker 398 (33%)
Quantity of alcohol consumption n (%)
- Less than 40 gram per day 566 (47%)
- 40 to 80 grams per day 268 (22%)
- more than 80 gram per day 384 (32%)
Diabetic mellitus n (%) 503 (41%)
Interventions for CP n (%)
- Patients with surgical interventions 385 (32%) - Patients with endoscopic interventions 477 (39%)
Response rate follow-up questionnaire (%)
Follow-up year 1**
- Responded - Non-responders - Withdrew from study - Deceased N = 780 660 (84.6%) 61 (51%) 36 (30%) 23 (19%) Follow-up year 2*** - Responded - Non-responders - Withdrew from study - Deceased N=429 350 (82%) 44 (56%) 26 (33%) 9 (11%) * Based on all eligible patients.
** Based on patients included in the first two years of CARE (from February 2010 to January 2012) *** Based on patients included in the first year of CARE (from February 2010 to January 2011)
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Table 3. Characteristics of hospitals participating in CARE as of July 2013Hospital Place Role in region (Academic vs. Community)
Participating
specialities Size (no. of beds)
Erasmus Medisch Centrum Rotterdam A GE, Surgery 1350
Universitair Medisch Centrum Groningen Groningen A GE 1339
UMC Utrecht Utrecht A GE, Surgery 1042
Academisch Medisch Centrum Amsterdam A GE, Surgery 1002
UMC St Radboud Nijmegen A GE, Surgery 953
Leids Universitair Medisch Centrum Leiden A GE, Surgery 882
Maastricht Universitaire Medisch Centrum Maastricht A GE, Surgery 715
VU Medisch Centrum Amsterdam A Surgery 713
St. Antonius Ziekenhuis Nieuwegein C GE, Surgery 1102
Ziekenhuis Groep Twente Almelo, Hengelo C GE 1085
Medisch Spectrum Twente Enschede C GE 1070
Isala Zwolle C GE, Surgery 994
Rijnstate Arnhem, Zevenaar C GE 955
Amphia ziekenhuis Breda C GE 854
Medisch Centrum Haaglanden Den Haag C GE 785
Jeroen Bosch Ziekenhuis ‘s-Hertogenbosch C GE 715
Gelre ziekenhuizen Apeldoorn Apeldoorn C GE, Surgery 708
Catharina Ziekenhuis Eindhoven C GE 696
Canisius-Wilhelmina Ziekenhuis Nijmegen C GE, Surgery 663
HagaZiekenhuis Den Haag C GE 660
Reinier de Graaf Groep Delft C GE, Surgery 622
Maasstad Ziekenhuis Rotterdam C GE 621
Meander Medisch Centrum Amersfoort C GE 587
Martini Ziekenhuis Groningen C GE 580
Onze Lieve Vrouwe Gasthuis Amsterdam C GE 555
Spaarne Ziekenhuis Hoofddorp C GE 540
Ziekenhuis Gelderse Vallei Ede C GE 510
VieCuri Medisch Centrum Venlo C GE 474
Bernhoven Uden C GE 460
Orbis Medisch Centrum Geleen C GE 425
St Jansdal Ziekenhuis Harderwijk C GE 341
Ziekenhuis Bronovo Den Haag C MDL 300
Medisch Centrum de Veluwe* Apeldoorn C GE -* Specialized gastroenterology clinic providing clinic visits and day care endoscopic treatments.
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