ORIGINAL ARTICLE
Management of Alcohol Use Disorders in Patients with Chronic Pancreatitis
Margareta B Lang1, Ralf Segersvärd1, Måns Grundsten1, Märta Segerdahl2, Urban Arnelo1, Johan Permert1, Johan Franck3, Matthias Löhr1, Jon A Tsai1
Divisions of 1Surgery and 2Anesthesiology, (CLINTEC), “Karolinska Institutet” and Karolinska University Hospital; 3Department of Clinical Neuroscience, “Karolinska Institutet”. Stockholm, Sweden
ABSTRACT
Context The outcome of treatment for patients with chronic pancreatitis may be improved by multidisciplinary management. Objective To study patients with chronic pancreatitis, especially regarding alcohol use, within a multi disciplinary program. Main outcome measures Prospective assessment at baseline and follow-up of alcohol use disorders using DSM-IV criteria, AUDIT score, interview-based quantification of alcohol intake and the biomarker for alcohol use s-CDT in patients referred because of chronic pancreatitis together with retrospective classification with the M-ANNHEIM risk factor analysis and severity scoring for chronic pancreatitis. Results Sixty patients (95%) of 63 consecutively included patients were classified as having chronic pancreatitis. Forty-four of these (73%) were available for follow-up evaluation, which took place after a minimum of 1 year (median 3 years). Alcohol consumption decreased at follow-up and no patients had ongoing alcohol dependence (P<0.001) as compared to 10 (23%) at initial evaluation. Patients with harmful alcohol use (AUDIT score ≥8 points) and pathological s-CDT had a reduction in both parameters (P=0.004 and P=0.063, respectively). Pain score according to M-ANNHEIM was unchanged, whereas use of analgesics decreased (P=0.005). Conclusions This feasibility study of patients with chronic pancreatitis demonstrated that multidisciplinary management seems to give a positive and sustainable effect on alcohol abuse and may be a useful concept for optimal classification, selection and treatment of patients with chronic pancreatitis.
INTRODUCTION
Chronic pancreatitis is a heterogeneous and progressive inflammatory disease characterized by pain and failure of exocrine and endocrine function in the pancreas [1]. Previous or ongoing over-consumption of alcohol has been described as a contributing etiological factor in 55-90% of all cases [2, 3, 4]. Despite the modest reported incidence from population-based studies in selected industrialized countries (5.4-8.6/100.000 per year) [5], chronic pancreatitis is associated with decades of substantial morbidity [6, 7]. In alcoholic chronic pancreatitis there is also a risk for an enhanced progression of the disease and problems specifically related to alcohol addiction [8, 9, 10]. Management of mild forms of chronic pancreatitis consists of avoiding triggering factors (i.e., alcohol, nicotine and high-fat diets), treatment of pain and substitution of exocrine and endocrine insufficiency [11]. In patients where conservative treatment is insufficient and/or in cases with complications in adjacent organs, e.g. duodenal or bile duct obstruction, surgical intervention may be considered [12]. In general, the long term results for surgery are superior to endoscopic treatment [13, 14], but endoscopic can be indicated in selected cases as a temporary treatment, since it does not preclude subsequent surgery, and as a definite treatment, in patients who are unfit for surgery [15]. Endoscopy may also be used to drain the commonly occurring pseudocysts in chronic pancreatitis, using transpapillary or transmural routes with complete cyst resolution in 65-92% of all cases [16].
In addition to addressing anatomical, endocrine and exocrine complications, alcohol addiction in chronic pancreatitis needs special attention. Firstly, the diagnosis of alcohol addiction is not always straightforward. Secondly, cessation of alcohol over-consumption is of benefit not only for general health and quality of life, but also after surgery, since ongoing alcohol abuse is a strong risk factor for complications and poorer ability to cope with postoperative pain [17, 18]. One month of preoperative abstinence was sufficient to reduce the postoperative morbidity in a randomized trial of patients with alcohol abuse undergoing colorectal surgery [19]. However, in clinical guidelines and routine clinical management, measures against excessive alcohol intake are often lacking [20].
In 2005, a new concept for management of chronic pancreatitis was introduced at our department. The patients undergo separate and a joint assessment by pancreatologists together with specialists in addiction medicine and pain management. The objectives of this concept were to identify the etiology of the disease, to deliver optimal conservative, endoscopic or surgical treatment and to specifically address issues related to alcohol. The aim of the current study was to evaluate the feasibility of such multidisciplinary management for chronic pancreatitis, aimed at assessment of and intervention for alcohol use disorders, using a combination of M-ANNHEIM classification of chronic pancreatitis [21], together with the fourth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) addiction criteria.
MATERIALS AND METHODS
Patients
Sixty-three consecutive patients referred between October 2005 and May 2009 with suspected chronic pancreatitis (i.e. no suspicion of pancreatic malignancy and signs of chronic pancreatitis in the pancreatic parenchyma or pancreatic ducts according to CT or MRT) and a clinical history of recurrent pancreatitis or abdominal pain. Patients unable to comply with the concept of interviews and questionnaires were excluded. After individual assessment by pancreatologists, addiction and pain specialists, a treatment plan was set up.
Study Enrolment (Figure 1)
Of the 63 patients, the diagnosis of chronic pancreatitis were confirmed in 60 cases (95.2%), and of these 44 were available for a follow-up evaluation, which took place after a median time of 3 (range: 2-4) years. Four patients had died, one had emigrated, two refused to participate further in the study, and one needed an interpreter who was not available. Three patients did not fulfill the diagnostic criteria for chronic pancreatitis at the initial evaluation and additional eight patients did not respond. The follow-up frequency was thus 73.3% of those who had chronic pancreatitis.
|
Figure 1. Study enrollment: summary of patient inclusion. |
Pancreatological Evaluation and Management
Pancreatological parameters were classified according to the M-ANNHEIM system [21]. M-ANNHEIM was first introduced at our clinic in 2008 and the initial evaluation of the patients was therefore done retrospectively with this modality. Each letter in M-ANNHEIM represents a risk factor: (M=multiple, A=alcohol, N=nicotine, N=nutrition, H=hereditary, E=efferent duct factors, I=immunological, M=miscellaneous). The severity of chronic pancreatitis was classified with the M-ANNHEIM scoring system, which consists of 0-4 points for reported pain, pain control usage, endoscopic and surgical intervention, endocrine insufficiency, exocrine insufficiency, morphological status according to pancreatic imaging and severe organ complications. Scores for the different symptoms and interventions were analyzed separately as well as combined in a total score. In addition, age, sex and body mass index (BMI) were registered [22]. Surgical (n=13) or endoscopic intervention (n=19) was done when indicated and the remaining patients were managed conservatively.
Addiction Evaluation and Management
Prior to the appointment, the patients were asked to fill out the Alcohol Use Disorder Identification Test (AUDIT), which estimates drinking habits over the last twelve months. The ten questions in AUDIT result in a total score of 0-40 points. To receive an acceptable sensitivity and specificity in this selected group of patients, we used the recommended cut-off value of ≥8 points as an indicator for problematic drinking [23]. The interview instrument “Timeline follow-back” was used to obtain the past 90 days data on the quantity and frequency of the patient’s alcohol consumption to average daily drinking in grams of alcohol per day [24]. Serum carbohydrate-deficient transferrin (s-CDT) is a biological marker for alcohol over-consumption. s-CDT detects the effect of regular alcohol consumption of at least 60 grams per day over a period of two weeks and is a marker with high specificity for alcohol over-consumption. The half-life for s-CDT is around two weeks provided no further alcohol consumption and the reference value is less than 2% [25, 26]. AUDIT, alcohol consumption and s-CDT was used to help determine if the patient has an alcohol addiction diagnosis according to DSM-IV, but the diagnosis is set by the clinician that interviewed the patient. The patients in this study were divided into four groups regarding alcohol addiction and alcohol consumption as follows:
A) neither history of alcohol addiction nor alcohol over-consumption, defined as never having fulfilled ≥3 DSM-IV criteria and no alcohol-induced chronic pancreatitis according to patient records (n=18);
B) previous alcohol-induced acute pancreatitis, but no addiction to alcohol, defined as no history of a DSM-IV addiction diagnosis, more than 12 months not fulfilling any of DSM-IV criteria for addiction, but a history of alcohol-induced acute pancreatitis (n=5);
C) alcohol addiction in remission, defined as a history of a DSM-IV addiction diagnosis and more than 12 months having passed without fulfilling ≥3 of DSM-IV criteria (n=11);
D) ongoing alcohol addiction, defined as ≥3 DSM-IV criteria fulfilled within the last 12 months (n=10).
All patients met with an addiction specialist at the time of initial evaluation and got a thorough assessment of their current alcohol consumption and general information about alcohol addiction. The ten patients classified as having an ongoing alcohol addiction were offered further appointments. Six of these patients agreed upon participation and were offered validated therapies consisting of medication (disulfiram, acamprosat, naltrexon) [27, 28] in combination with the validated treatment methods of “Motivational Interviewing” [29], or “Relapse Prevention” [30, 31, 32]. “Motivational Interviewing” is a set of techniques and a counseling style focused to identifying and mobilizing the patient’s intrinsic values and goals to stimulate behavioral change and “Relapse Prevention” consists of both a conceptual model of relapse and cognitive and behavioral strategies to prevent or limit relapse episodes. No specific intervention was performed against smoking.
Follow-up Evaluation
After a minimum time period of twelve months, all data collection was repeated at a follow-up visit.
ETHICS
The Regional Ethics Committee reviewed this project and classified it as being a quality control and thus outside the scope of the Committee; therefore, the informed consent was not needed. The patients were treated according to the ethical guidelines of the “World Medical Association (WMA) Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects” adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964 and amended by the 59th WMA General Assembly, Seoul, South Korea, October 2008.
STATISTICS
The data is presented as median and interquartile range (IQR). The Wilcoxon signed rank test for comparison of paired data was used for comparing changes between initial evaluation and follow-up. Comparisons of addiction and alcohol over-consumption were done by the McNemar test. Two tailed P values less than 0.05 were considered as statistically significant. Sigma Stat software (Jandel, San José, CA, USA) was used for all calculations.
RESULTS
Study Demographics and M-ANNHEIM Risk Factor Analysis (Table 1)
A risk factor analysis according to the M-ANNHEIM classification system and basic demographic data was available for all 44 subjects. A majority of the study population had more than one risk factor (32 subjects, 72.7%). The most common risk factor was smoking (39 subjects, 88.6%) and 29 (74.4%) of the smokers had ≥20 pack years. Twenty-six of the 44 patients (59.1%) were classified as having alcohol consumption as the most likely contributing cause to their chronic pancreatitis. For the remainder of the M-ANNHEIM risk factor analysis the results were as follows: one patient (2.3%) had “Immunology” as a risk factor due to Crohn’s disease. Three cases (6.8%) had “Nutrition” as a risk factor, all had hyperlipidemia. Six patients (13.6%) had partial (n=1) or complete (n=5) pancreas divisum, who were classified as having “Efferent duct factor” as a risk factor, and the 6 patients (13.6%) with “Hereditary” as risk factor had either familial chronic pancreatitis or early/late-onset idiopathic chronic pancreatitis. Two patients (4.5%) were classified with “Miscellaneous” risk factor; prior to the first episode of acute pancreatitis, 1 (2.3%) had chronic renal failure and 1 (2.3%) was diagnosed with hypercalcemia.
|
Table 1. Demographics and risk factor profile. |
|
|
Age (years) a |
|
|
Male gender b |
33 (75.0%) |
|
BMI (m/kg2) a |
|
|
|
|
|
M-ANNHEIM risk factors b |
|
|
a median and interquartile range b frequencies |
|
M-ANNHEIM Severity Scores (Table 2)
Forty-three patients (97.7%) were available at follow-up. Between initial evaluation and follow-up, the total median M-ANNHEIM score increased from 11 to 12 (P=0.001), but the reported use of analgesics decreased from 2 to 1 (P=0.005). Exocrine insufficiency and thus also enzyme supplementation, which is included in the definition of exocrine insufficiency according to M-ANNHEIM, increased between the initial evaluation and follow-up (P=0.027), even though the median values were the same. There was a borderline significant increase in number of patients with diabetes mellitus at follow-up compared to the initial evaluation (12 vs. 7 patients, P=0.063). The number of patients that had a potentially reversible organ complication increased from 12 to 15 and the number of cases with irreversible splenic or portal vein thrombosis increased from 4 to 8 (P=0.016 for all organ complications combined).
|
Table 2. M-ANNHEIM: separate dimensions and total score. |
|||||||||||||||
|
|
Initial evaluation (n=44) |
|
Follow-up (n=43 a) |
|
P value b |
||||||||||
|
0 |
1 |
2 |
3 |
4 |
median (IQR) |
0 |
1 |
2 |
3 |
4 |
median (IQR) |
||||
|
Patient report of pain |
3 |
12 |
8 |
13 |
8 |
2 (1-3) |
|
13 |
4 |
6 |
7 |
13 |
2 (0-4) |
|
0.640 |
|
Use of analgesics |
6 |
11 |
27 |
|
|
2 (1-2) |
|
16 |
9 |
18 |
|
|
1 (0-2) |
|
0.005 |
|
Endocrine insufficiency |
37 |
|
|
|
7 |
0 (0-0) |
|
31 |
|
|
|
12 |
0 (0-4) |
|
0.063 |
|
Exocrine insufficiency |
16 |
2 |
26 |
|
|
2 (0-2) |
|
8 |
5 |
30 |
|
|
2 (1-2) |
|
0.027 |
|
Organ complications |
28 |
|
12 |
|
4 |
0 (0-2) |
|
20 |
|
15 |
|
8 |
1 (0-2) |
|
0.016 |
|
Endoscopic intervention |
30 |
|
14 |
|
|
0 (0-2) |
|
25 |
|
19 |
|
|
0 (0-2) |
|
0.063 |
|
Surgical intervention |
42 |
|
|
|
2 |
0 (0-0) |
|
29 |
|
|
|
15 |
0 (0-4) |
|
<0.001 |
|
Total |
162 |
26 |
89 |
16 |
25 |
11 (9-12) |
|
142 |
19 |
90 |
10 |
52 |
12 (9.5-16) |
|
0.001 |
|
IQR: interquartile range a Information about surgical intervention was available for all 44 patients. b Wilcoxon matched-pairs test |
|||||||||||||||
Use of Alcohol and Alcohol Addiction (Table 3)
At follow-up, no patients had an ongoing alcohol addiction (group D) and all these patients instead fulfilled criteria for group C, i.e. alcohol addiction in remission (P<0.001). There were no changes in the other groups.
|
Table 3. Alcohol use and addiction. |
|||
|
Alcohol use and drinking habits |
Initial evaluation (n=44) |
Follow-up |
P value |
|
A. Neither any history of alcohol addiction nor alcohol overconsumption |
18 (40.9%) |
18 (40.9%) |
|
|
B. Alcohol over-consumption in remission |
5 (11.4%) |
5 (11.4%) |
|
|
C. Alcohol addiction in remission |
11 (25.0%) |
21 (47.7%) |
0.002 a |
|
D. Ongoing alcohol addiction |
10 (22.7%) |
0 |
0.002 a |
|
a McNemar test calculated by taking into account groups C and D only because there were no changes in the other two groups. |
|||
Alcohol Use Disorder Identification Test (AUDIT; Figure 2)
Forty-two patients were available at follow-up. The median score of the patients with a total AUDIT score of ≥8 points at the initial evaluation (median, IQR: 14, 9-22; n=10) had significantly (P=0.004) decreased at follow-up (median, IQR: 0, 0-1; n=9). No significant change was found in the other 32 patients with AUDIT score less than 8 (data not shown).
|
Figure 2. Alcohol Use Disorder Identification Test (AUDIT) at initial evaluation and follow-up among the 10 subjects with problematic drinking (³8 points) at initial evaluation (data of one subject was not available at follow-up). |
Serum carbohydrate-deficient transferrin (s-CDT; Figure 3)
Follow-up samples were available in 36 patients. Among the patients with pathological s-CDT levels (≥2%, n=6) at initial evaluation a trend toward a significantly lower value at follow-up was observed (median, IQR: 4.3%, 2.5-6.6% vs. 1.6%, 0.7-2.7%; P=0.063). No significant change was found in the other 30 patients with normal s-CDT basal values (data not shown).
|
Figure 3. Serum carbohydrate deficient transferring (s-CDT) at initial evaluation and follow-up among the 6 subjects with pathological value (³2.0%) at initial evaluation. |
Quantification of Alcohol Consumption (Figure 4)
Among the 10 patients classified as having an ongoing addiction (group D) at initial evaluation alcohol consumption had significantly decreased at follow-up (median, IQR: 4.4, 2.1-28 g/day vs. 0, 0-0 g/day; P=0.018).
|
Figure 4. Alcohol consumption among the 10 patients of group D at initial evaluation and follow-up, estimated with the time-line follow back instrument. |
DISCUSSION
Previous or ongoing over-consumption of alcohol is an important factor in the pathogenesis of both acute and chronic pancreatitis and addiction to alcohol is also common among these patients [2, 3, 4]. Despite this, studies on interventions for alcohol abuse in this population are scarce [20]. In a recent trial specific interventions against harmful alcohol use resulted in a reduction of episodes with alcoholic acute pancreatitis [33]. By introducing a multidisciplinary group consisting of pancreatologists, addiction and pain specialists, we aimed to improve the outcome of both interventional and conservative treatment for the complex group of patients with chronic pancreatitis. There was an obvious selection of patients given that all were referrals. However, all patients complied with the initial evaluation and the follow-up frequency was also reasonably high (73%), only 2 patients (3%) actually refused to participate in follow-up and 8 (13%) did not respond. In this patient cohort, we found that all who had an ongoing alcohol use disorder according to DSM-IV at the initial evaluation were in remission at follow-up. Furthermore, self-reported data implying problem drinking (AUDIT) and quantification of alcohol intake decreased, and there was also a trend towards lower levels of s-CDT, a biomarker for alcohol use. Alcohol addiction has scarcely been investigated in earlier studies of chronic pancreatitis. Addiction was generally managed successfully herein, based on the different modalities for evaluation that we applied. The special circumstances in patients with chronic pancreatitis and an alcohol use disorder, i.e. somatic symptoms such as recurrent or chronic pain as well as gastrointestinal and metabolic manifestations, may have facilitated the successful cessation of alcohol abuse, possibly as a result of the multidisciplinary management.
The M-ANNHEIM multiple risk factor classification and scoring system was applied for clinical classification of the patients according to the etiology and the severity of chronic pancreatitis [3]. M-ANNHEIM also includes rare risk factors and the treatment options and prognosis may therefore be better evaluated. The current study demonstrates that the etiology of chronic pancreatitis often is multifactorial. Historically, alcohol addiction has been recognized as the major risk factor for chronic pancreatitis. In contrast, several recent studies [5, 34], including the present, show that alcohol abuse might be less frequent than previously reported and that smoking may be an independent risk factor for chronic pancreatitis. Although selection bias might contribute to the relatively low number of patients with a history of harmful alcohol use in the present sample, due to reluctance to referral or follow-up, the systematic assessment of alcohol use disorders suggests that the incidence of alcohol abuse was in the same range as reported in other cohorts [34].
The M-ANNHEIM scoring system also estimates the severity of chronic pancreatitis and due to the progressive character of the disease, the total score increases over time [21]. The M-ANNHEIM assessment presented here should be interpreted with some caution as scoring was made retrospectively and in most cases no new imaging was indicated from a clinical perspective, leaving the scoring of the pancreas morphological status arbitrarily unchanged. Furthermore, exocrine and endocrine insufficiency was assessed only by clinical presentation and not by laboratory testing, which may have underestimated these parameters. Nevertheless, when comparing the separate dimensions of the M-ANNHEIM scoring initially and at follow-up, we observed an increase in the use of enzyme supplementation and a decrease in the use of analgesics. The decreased need for analgesics and particularly the combination of a stable degree of pain and decreased consumption of analgesics indicates that the total pain burden may have decreased. Increased enzyme substitution as well as endoscopic and/or surgical intervention or psychological factor (e. g. attention from a pain specialist) could all have contributed to the reduced need for analgesics.
In conclusion, the multidisciplinary management model presented here, which includes thorough evaluation and intervention jointly by pancreatologists, addiction and pain specialists, is feasible and seems to have potential for providing a sustainable effect on alcohol use disorders among patients with chronic pancreatitis.
Received July 11th, 2012 – Accepted October 15th, 2012
Key words Alcohol-Related Disorders; Pancreatitis, Chronic
Abbreviations AUDIT: Alcohol Use Disorder Identification Test; CDT: carbohydrate-deficient transferrin; DSM: Diagnostic and Statistical Manual of Mental Disorders
Conflict of interest The authors declare no conflict of interest
Correspondence
Jon
Tsai
Karolinska University Hospital Huddinge K53
14186 Stockholm
Sweden
Phone: +46-8.5858.2307
Fax: +46-8.5858.6910
E-mail: jon.tsai@ki.se
References
1. Witt H, Apte MV, Keim V, Wilson JS. Chronic pancreatitis. Challenges and advances in pathogenesis, genetics, diagnosis, and therapy. Gastroenterology 2007;132:1557-1573. [PMID 17466744]
2. Tattersall SJN, Apte MV, Wilson JS. A fire inside: Current concepts in chronic pancreatitis. Intern Med J 2008;38:592-598. [PMID 18715303]
3. Schneider A, Singer MV. Alcoholic pancreatitis. Dig Dis 2005;23:222-231. [PMID 16508286]
4. Pezzilli R, Morselli-Labate AM. Alcoholic pancreatitis: Pathogenesis, incidence and treatment with special reference to the associated pain. Int J Envir Res Public Health 2009 6:2763–2782. [PMID 20049222]
5. Yadav D, Whitcomb DC. The role of alcohol and smoking in pancreatitis. Nat Rev Gastroenterol Hepatol 2010;7:131-145. [PMID 201250919
6. Ammann RW, Akovbiantz A, Largiader F, Schueler G. Course and outcome of chronic pancreatitis. Gastroenterology 1984;86:820-828. [PMID 6706066]
7. Lankisch PG, Löhr-Happe A, Otto J, Creutzfeldt W. Natural course in chronic pancreatitis. Digestion 1993;54:148-155. [PMID 8359556]
8. Ammann RW. Diagnosis and management of chronic pancreatitis: Current knowledge. Swiss Medi Wkly 2006;136:166-174. [PMID 16633964]
9. Spanier BWM, Dijkgraaf MGW, Bruno MJ. Epidemiology, aetiology and outcome of acute and chronic pancreatitis: An update. Best Pract Res Clin Gastroenterol 2008;22:45-63. [PMID 18203812]
10. Wehler M, Reulbach U, Nichterlein R, Lange K, Fischer B, Farnbacher M et al. Health related quality of life in chronic pancreatitis. A psychometric assessment. Scand J Gastroenterol 2003;38:1083-1089. [PMID 14621285]
11. Pfützer RH, Schneider A. Treatment of alcoholic pancreatitis. Dig Dis 2005;23:241-246. [PMID 16508288]
12. Strobel O, Büchler MW, Werner J. Surgical therapy of chronic pancreatitis: Indications, techniques and results. Int J Surg 2009;7:305-312. [PMID 19501199]
13. Cahen DL, Gouma DJ, Nio Y, Rauws EAJ, Boermeester MA, Busch OR et al. Endoscopic versus surgical drainage of the pancreatic duct in chronic pancreatitis. N Engl J Med 2007; 356: 676-684. [PMID 17301298]
14. Díte P, Ružicka M, Zboril V, Novotný I. A prospective, randomized trial comparing endoscopic and surgical therapy for chronic pancreatitis. Endoscopy 2003;35:553-558. [PMID 12822088]
15. Rösch T, Daniel S, Scholz M, Huibregtse K, Smits M, Schneider T et al. Endoscopic treatment of chronic pancreatitis: A multicenter study of 1000 patients with long-term follow-up. Endoscopy 2002;34:765-771. [PMID 22244496]
16. Aghdassi AA, Mayerle J, Kraft M, Sielenkamper AW, Heidecke CD, Lerch M. Diagnosis and treatment of pancreatic pseudocysts in chronic pancreatitis. Pancreas 2008;36:105-112. [PMID 18376299]
17. Kork F, Neumann T, Spies C. Perioperative management of patients with alcohol, tobacco and drug dependency. Curr Opin Anaesthesiol 2010;23:384-390. [PMID 20404723]
18. van Loo ES, van Baal MCPM, Gooszen HG, Ploeg RJ, Nieuwenhuijs VB. Long-term quality of life after surgery for chronic pancreatitis. Br J Surg 2010;97:1079–1086. [PMID 20632275]
19. Toennesen H, Rosenberg J, Nielsen HJ, Rasmussen V, Hauge C, Pedersen IK et al. Effect of preoperative abstinence on poor postoperative outcome in alcohol misusers: Randomised controlled trial. BMJ 1999;318:1311-1316. [PMID 10323814]
20. Apte MV, Pirola RC, Wilson JS. Pancreas: Alcoholic pancreatitis-it's the alcohol, stupid. Nat Rev Gastroenterol Hepatol 2009;6:321-322. [PMID 19494819]
21. Schneider A, Löhr JM, Singer MV. The m-annheim classification of chronic pancreatitis: Introduction of a unifying classification system based on a review of previous classifications of the disease. J Gastroenterol 2007;42:101-119. [PMID 17351799]
22. Mokrowiecka A, Pinkowski D, Malecka-Panas E, Johnson CD. Clinical, emotional and social factors associated with quality of life in chronic pancreatitis. Pancreatology 2010;10:39-46. [PMID 20332660]
23. Babor TF, Higgins-Biddle JC, Saunders JB, Maristela GM. Audit - the alcohol use disorders identification test guidelines for use in primary care. In: Dependence DoMHaS (ed), The World Health Organization (WHO), 2001, pp 10-20.
24. Sobell LC, Agrawal S, Annis H, Ayala-Velazquez H, Echeverria L, Leo GI et al. Cross-cultural evaluation of two drinking assessment instruments: Alcohol timeline followback and inventory of drinking situations. Subst Use Misuse 2001;36:313-331. [PMID 11325169]
25. Anton RF. Carbohydrate-deficient transferrin for detection and monitoring of sustained heavy drinking: What have we learned? Where do we go from here? Alcohol 2001;25:185-188. [PMID 11839464]
26. Heilig M, Wisén O. Beroendetillstånd. Studentlitteratur AB, Lund, Sweden; 2004.
27. Streeton C, Whelan G. Naltrexone, a relapse prevention maintenance treatment of alcohol dependence: A meta-analysis of randomized controlled trials. Alcohol Alcohol 2001;36:544-552. [PMID 11704620]
28. Soyka M, Rösner S. Emerging drugs to treat alcoholism. Expert Opinion on Emerging Drugs 2010;0:1-17. [PMID 20560783]
29. Rubak S, Sandbaek A, Lauritzen T, Christensen B. Motivational interviewing: A systematic review and meta-analysis. Br J Gen Pract 2005;55:305-312. [PMID 15826439]
30. Marlatt GA, Baer JS, Kivlahan DR, Dimeff LA, Larimer ME, Quigley LA et al. Screening and brief intervention for high-risk college student drinkers: Results from a 2-year follow-up assessment. J Consult Clin Psychol 1998;66:604-615. [PMID 9735556]
31. Larimer ME, Palmer RS, Marlatt GA. Relapse prevention, an overview of marlatt’s cognitive-behavioral model. Alcohol Res Health 1999;23:151-160. [PMID 10890810]
32. Irvin JE, Bowers CA, Dunn ME, Wang MC. Efficacy of relapse prevention: A meta-analytic review. J Consult Clin Psychol 1999;67(4):563-570. [PMID 10450627]
33. Nordback I, Pelli H, Lappalainen-Lehto R, Jarvinen S, Raty S, Sand J. The recurrence of acute alcohol-associated pancreatitis can be reduced: A randomized controlled trial. Gastroenterology 2009;136:848-855. [PMID 19162029]
34. Coté GA, Yadav D, Slivka A, Hawes RH, Anderson MA, Burton FR et al. Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis. Clin Gastroenterol Hepatol 2011;9:266-273. [PMID 21029787]