der
Medizinischen Hochschule Hannover
Die Langzeitergebnisse nach Pankreasoperation bei chronischer Pankreatitis zeigen ein besseres Überleben für
die Patienten ohne Insulinabhängigkeit und mit Pankreasenzymersatztherapie
Dissertation zur Erlangung des Doktorgrades der Zahnmedizin in der Medizinischen Hochschule Hannover
vorgelegt von Vagia Paroglou aus Holzminden
Hannover 2014
am 03.12.2014
Gedruckt mit Genehmigung der Medizinischen Hochschule Hannover.
Präsident: Prof. Dr. med. Christopher Baum Betreuer der Arbeit: PD. Dr. med. Harald Schrem Referent: Prof. Dr. med. Hans-Rudolf Raab Korreferent: Prof. Dr. med. Michael Neipp
Tag der mündlichen Prüfung: 03.12.2014
Promotionsausschussmitglieder: Prof. Dr. med. Christian Krettek Prof. Dr. med. Hans-Rudolf Raab
Prof. Dr. med. vet. Dirk Berens von Rautenfeld
1.
Winny M, Paroglou V, Bektas H, Kaltenborn A, Reichert B, Zachau L, Kleine M, Klempnauer J, Schrem H. Insulin dependence and pancreatic enzyme replacement therapy are independent prognostic factors for long-term survival after operation for chronic pancreatitis. Surgery. 2014 Feb;155(2):271-9. doi:
10.1016/j.surg.2013.08.012. Epub 2013 Nov 25
2. Zusammenfassung, inklusive entsprechendem Literaturverzeichnis
3. Lebenslauf
4. Erklärung nach §2 Abs. 2 Nrn. 6 und 7 PromO
enzyme replacement therapy are independent prognostic factors for long-term survival after operation for chronic pancreatitis
Markus Winny, MD,aVagia Paroglou,aH€useyin Bektas, MD,aAlexander Kaltenborn,a,b
Benedikt Reichert, MD,a,cLea Zachau, MD,aMoritz Kleine, MD,aJ€urgen Klempnauer, MD,aand Harald Schrem, MD,aHannover and Kiel, Germany
Background.This retrospective, single-center, observational study on postoperative long-term results aims to define yet unknown factors for long-term outcome after operation for chronic pancreatitis.
Patients and Methods.We analyzed 147 consecutive patients operated for chronic pancreatitis from 2000 to 2011. Mean follow-up was 5.3 years (range, 1 month to 12.7 years). Complete long-term survival data were provided by the German citizen registration authorities for all patients. A quality-of- life questionnaire was sent to surviving patients after a mean follow-up of 5.7 years.
Results.Surgical principles were resection (n= 86; 59%), decompression (n= 29; 20%), and hybrid procedures (n= 32; 21%). No significant influences of different surgical principles and operative procedures on survival, long-term quality of life and pain control could be detected. Overall 30-day mortality was 2.7%, 1-year survival 95.9%, and 3-year survival 90.8%. Multivariate Cox regression analysis revealed that only postoperative insulin dependence at the time of hospital discharge (P= .027;
Exp(B) = 2.111; 95% confidence interval [CI], 1.089–4.090) and the absence of pancreas enzyme replacement therapy at the time of hospital discharge (P= .039; Exp(B) = 2.102; 95% CI, 1.037–
4.262) were significant, independent risk factors for survival with significant hazard ratios for long- term survival. Long-term improvement in quality of life was reported by 55 of 76 long-term survivors (73%).
Conclusion.Pancreatic enzyme replacement should be standard treatment after surgery for chronic pancreatitis at the time of hospital discharge, even when no clinical signs of exocrine pancreatic failure exist. This study underlines the potential importance of early operative intervention in chronic pancreatitis before irreversible endocrine dysfunction is present. (Surgery 2014;155:271-9.)
From the General, Visceral and Transplantation Surgery,aHannover Medical School, and the Federal Armed Forces Medical Center Hannover,bHannover; and the Department of General and Thoracic Surgery,cUni- versit€atsklinikum Schleswig Holstein, Kiel, Germany
CHRONIC PANCREATITIS is a progressive and painful benign inflammatory process of the pancreas during which pancreatic secretory tissue is destroyed and re- placed by fibrous tissue leading to pancreatic exocrine and endocrine insufficiency.1-3 Pain in
the form of recurrent attacks of pancreatitis or con- stant and disabling pain is usually the main symp- tom.1-3 Management of pain is mainly empirical, involving analgesics and duct drainage by endo- scopic or operative intervention, including partial or total pancreatectomy.2 Medical treatment of intractable pain fails frequently owing to narcotic de- pendency and failure to control pain effectively.3 The most frequent indication leading to surgery is triggered by otherwise intractable pain.1-3 The main goals of operative intervention for chronic pancreatitis are to relieve pain and preserve pancre- atic function.1-3These 2 goals may be conflicting in cases treated with pancreatic resection. Operative procedures have the known potential to provide
M.W. and V.P. contributed equally to this paper.
Accepted for publication August 12, 2013.
Reprint requests: Harald Schrem, MD, Allgemein-, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hann- over, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. E-mail:
schrem.harald@mh-hannover.de.
0039-6060/$ - see front matter Ó2014 Mosby, Inc. All rights reserved.
http://dx.doi.org/10.1016/j.surg.2013.08.012
SURGERY 271
long-term pain relief and good postoperative quality of life along with less mortality and morbidity compared with nonoperative treatments.1
The differentiation of chronic pancreatitis and pancreatic cancer is crucial for choosing therapies and can be challenging in some cases.4,5Complica- tions of pancreatic surgery can lead to mortality and substantial morbidity, including insulin- dependent diabetes and exocrine pancreatic insuf- ficiency. Several studies have reported that local resection of the pancreatic head, with or without duct drainage, and duodenum-preserving pancre- atic head resection offer outcomes as effective as pancreatoduodenectomy, with less morbidity and mortality.3 The late incidences of recurrent pain, diabetes, and exocrine insufficiency were reported equivalent for all 3 operative approaches, which include decompression of the diseased and ob- structed pancreatic ducts, denervation of the pancreas; resection of the proximal, distal, or total pancreas; and hybrid procedures with combina- tions of decompression and limited resection.1-3 The current study examines our experience with operative intervention for chronic pancreatitis and aims to define yet unknown factors for long- term survival and quality of life after operation for chronic pancreatitis.
PATIENTS AND METHODS
The setting of the study is a tertiary referral center in a German university hospital. We included patients operated for chronic pancreatitis at our institution between January 2000 and January 2011. Preoperative symptoms summarized inTable Irepresent the indications for operation.
Therapeutic success was defined as survival with long-term relief of the major symptom pain. The local ethics committee for clinical studies approved the study protocol (reference number:
1,652–2,012). Exclusion criteria were preoperative suspicion of pancreatic cancer or postoperative his- topathologic detection of pancreatic cancer in the resection specimen.
Data collection.This retrospective, single-center analysis was completed by analysis of survival of the complete cohort in collaboration with the German registration authorities and an additional follow-up survey of long-term survivors. Data were analyzed by chart review. Mean follow-up was 5.3 years (range, 1 month to 12.7 years). Follow-up times were comparable between the 3 main operative interventions (decompression, resection, and hybrid procedures;P = .442).
Survival as the major study endpoint was carried out for all patients with complete information
from the registration authorities in Germany who provided information on patients’ current ad- dresses and survival status. In Germany, all changes of address and all deaths by law have to be reported to the registration authorities. This infor- mation is accessible for our institution within the current legal system in Germany. No patients were lost to follow-up with this approach, at least with respect to their survival status and current ad- dresses, because none of the patients moved abroad to another jurisdiction.
For follow-up, an abbreviated and slightly modi- fied version of the chronic pancreatitis module of the European Organization for Research and Treatment quality-of-life questionnaire was sent selectively to the current addresses of known long-term survivors. The questionnaire included questions on their clinical condition, occurrence Table I. Preoperative parameters of the study population
Parameter n %
Etiology
Alcohol abuse 70 47.5
Choledocho/cystolithisasis 7 4.8
Anatomic pancreatic duct variant 7 4.8
Duodenal diverticulum 3 2.1
Pancreatic duct stones 2 1.4
Unknown 58 39.4
Preoperative clinical symptoms
Pain 134 91.2
Diarrhea 16 10.9
Vomiting 34 23.1
Weight decrease 73 49.7
Night sweating 8 5.4
Jaundice 13 8.8
Preoperative treatment
Insulin dependency 27 18.4
Pancreas enzyme substitution 72 49.0
Papillotomy 46 31.3
Endoscopic bile duct stone removal
5 3.4
Bile duct dilatation 66 44.9
Bile duct stenting 31 21.1
Pancreatic duct stenting 20 13.6
Transgastric endoscopic drainage of pseudocyst
2 1.4
Preoperative laboratory parameters
(in serum) Mean Range
Amylase (U/L) 106 4–996
Lipase (U/L) 323 7–6,065
Bilirubin (mmol/L) 16 3–505
Carbohydrate antigen 19-9 (U/mL) 986 1–46,600 Carcinoembryonic antigen (ng/mL) 5 1–25
of malignant disease, diabetes, diarrhea, analgesic medication, food intolerance, body size and weight, professional reintegration, and improve- ment of quality of life and pain using visual analog scales (from 1 [no improvement] to 10 [immeasur- able improvement]). The questionnaire was sent to 112 long-term surviving patients after a mean time between operation and follow-up of 5.7 years (median, 5.6; range, 0.86–12.7); 76 of 112 patients answered the questionnaire and 35 patients (68%) died during follow-up after a mean time of 3.8 years (range, 1 month to 8.7 years).
Clinical, surgical, and demographic characteris- tics. There were 147 patients (97 males, 50 females) with a mean age of 50.5 years (range, 22–79) who met our inclusion criteria. The etiol- ogies leading to chronic pancreatitis, preoperative clinical symptoms, preoperative treatment, and preoperative laboratory parameters are summa- rized inTable I.
A total of 459 pathologic, anatomic character- istics were detected in 147 patients. Combinations of these characteristics are a frequent observa- tion. The combinations of morphologic changes and their anatomic location more or less dictated the chosen surgical principle and the operative procedure. The presence or absence of a preop- erative mass in the pancreatic head influenced the surgical principle and the chosen operative procedure (Table II). Taken together, 56 of 60 pa- tients with a mass in the pancreatic head were treated with a resection either alone or in combi- nation with a decompression procedure (93%)
and the remainder by a decompression proce- dure alone (7%).
Patients received pancreas enzyme replacement therapy with Kreon (median dose, 30,000 PhEur Units; range, 0–240,000) after operation and before discharge, depending on the presence of obvious clinical signs for exocrine pancreatic fail- ure. Patients who did not receive pancreas enzyme replacement were believed not to need this therapy.
Statistical methods. Kaplan-Meier estimates of survival with log-rank test, univariate and multivar- iate Cox regression analysis, univariate regression analysis, 2-sided Fisher’s exact tests, Mann–Whit- ney U tests, receiver operating characteristic (ROC) curve analysis, and chi-square tests were used as appropriate. The SPSS statistics software version 20.0 (IBM, Somers, NY) was used for statis- tical analysis.
RESULTS
Preoperative clinical symptoms and etiologies of chronic pancreatitis.Table Isummarizes the fre- quencies of preoperative clinical symptoms, preop- erative treatments, and the etiologies of chronic pancreatitis. Preoperative vomiting was associated with duodenal occlusion (P= .011, 2-sided Fisher’s exact test). Preoperative unintended weight decrease (>5 kg in>1one month) was associated with unsuccessful preoperative pain control (P = .002, 2-sided Fisher’s exact test).
Preoperative laboratory parameters. Preopera- tive laboratory parameters are summarized in Table II. Overview of the surgical principles and the operative procedures used in this study
Operative procedures n %
Decompression (n= 29; 20%)
Longitudinal pancreaticojejunostomy 25 17.0
Resection of duodenal diverticulum 1 0.7
Aneurysm resection of the splenic artery with arterial reanastomoses 1 0.7 Duodenotomy and papillotomy with removal of pancreatic ductal stones 2 1.4 Resection (n= 86; 59%)
Proximal pancreatoduodenectomy 59 40.1
Pylorus-preserving pancreatoduodenectomy 12 8.1
Distal pancreatectomy 9 6.1
Total pancreatectomy 6 4.1
Hybrid procedures (n= 32; 22%)
Duodenum-preserving pancreatic head resection 18 12.1
Local pancreatic head resection with longitudinal pancreaticojejunostomy 6 4.1 Proximal pancreatoduodenectomy with longitudinal pancreaticojejunostomy 4 2.8
Distal pancreatectomy with longitudinal pancreaticojejunostomy 1 0.7
Distal pancreatectomy with resection of duodenal diverticulum 1 0.7
Central pancreatectomy with proximal and distal pancreaticojejunostomy 2 1.4
Total 147 100
Table I. Preoperative amylase and lipase levels were unable to predict postoperative pain control at the time of hospital discharge or during long-term follow-up (area under the ROC curve <0.700).
The preoperative bilirubin level was unable to pre- dict postoperative quality of life during long-term follow-up (area under the ROC curve<0.700).
Role of the type of operative therapy. Applied surgical principles and procedures are summa- rized in Table II. Denervation procedures have not been performed in this series. A total of 128 patients required pancreatic ductal reconstruction (87%). After pancreatectomy (n= 86), reconstruc- tion in 40 patients was by pancreaticogastrostomy and in 31 patients by pancreaticojejunostomy (Table II).
The surgical principle (decompression versus resection versus hybrid procedures) had no influ- ence on the improvement of long-term quality of life (P = .617, Chi-square) or on the absence or improvement of pain during long-term follow-up (P= .282, Chi-square). The operative procedure it- self had also no influence on the improvement of long-term quality of life (P = .524, Chi-square), on the absence or improvement of pain during long- term follow-up (P = .463; Chi-square), or on pancreas enzyme replacement therapy at the time of hospital discharge (P= .367, Chi-square).
Analysis of the questionnaire results and the clinical data showed that the most frequently applied surgical procedures (longitudinal pancreaticojejunos- tomy, n = 25; proximal pancreatoduodenectomy, n = 59; pylorus-preserving pancreatoduodenectomy, n = 12; duodenum-preserving pancreatoduodenec- tomy,n = 18) had no influence on the frequencies of 30-day mortality, improved long-term, postopera- tive quality of life, professional long-term reintegra- tion, long-term opioid use postoperatively, long-term insulin dependence postoperatively, long-term body mass index (kg/m2), hospital stay in days and inten- sive care stay in days (P>.05, Chi-square and Mann- WhitneyUtest results).
Postoperative morbidity and reoperations.The median hospital stay was 20 days (range, 6–144) and the median intensive care stay 1 day (range, 1–
27). Reoperations during the hospital stay of the index operation were necessary in 14 cases (reop- eration rate, 9.5%): Resection of the rectum with surgical drainage of a perirectal abscess formation (n= 1), early incisional herniation requiring oper- ative repair (n = 2), cholecystectomy owing to acute cholecystitis after decompression procedures (n= 2), emergency operation for perforatedHelico- bacter pylori-positive gastric ulcer disease (n = 1), wound dehiscence (n= 4), and drainage of wound
infections (n= 4). Long-term complications associ- ated with chronic pancreatitis and/or its operative treatment included incisional herniation requiring later reoperation in 2 patients, pancreatitis in 13, and recurrent cholangitis in 9. Operative treat- ment for some of these long-term complications was associated with additional hospital admissions to our department or to other hospitals (hernia repair,n = 2; revision of the hepaticojejunostomy, n= 5; pancreatectomy, n= 3). Of 147 patients, 21 required operations unrelated to chronic pancrea- titis and/or its surgical treatment during long-term follow-up, including minor surgery for trauma and heart bypass surgery. Of 76 patients, 16 (21%) who answered the questionnaire required further hos- pital admissions without operative interventions af- ter their hospital stay of the index operation. For 19 of 76 patients (25%) who answered our ques- tionnaire, ongoing medical treatment for chronic pancreatitis was necessary during long-term follow-up.
Survival.Four of 147 patients died during their hospital stay leading to a hospital mortality rate of 2.7%. These 4 patients were treated by pancreato- duodenectomy, pylorus-preserving pancreatoduo- denectomy, total pancreatic resection, and distal pancreatectomy with additional resection of a duodenal diverticulum (n= 1 each). Causes of death were multiorgan failure secondary to sepsis in 2.
The 30-day mortality and hospital mortality were both 2.7%. The 1-year survival was 96% and 3-year survival 91%. Patient gender had no influence on long-term survival (P = .486, log-rank). The pres- ence of enlarged peripancreatic lymph nodes was associated with a worse long-term survival (P = .027; log-rank). Preoperative alcohol abuse had no influence on long-term survival (P = .726; log- rank). The necessity of subsequent reoperations had also no influence on long-term patient survival (P= .295; log-rank). Preoperative as well as postop- erative insulin dependency had a marked negative influence on postoperative long-term patient sur- vival (P = .007; log-rank;Fig 1).
Finally, 72 patients needed pancreas enzyme substitution preoperatively (49%), which had no influence on patient survival (P= .177; log-rank).
Multivariate Cox regression analysis revealed that only postoperative insulin dependence at hospital discharge (P = .027; Exp(B) = 2.111;
95% confidence interval, 1.089–4.090) and the lack of pancreas enzyme replacement therapy at hospital discharge (P = .039; Exp(B) = 2.102;
95% confidence interval, 1.037–4.262) were inde- pendent risk factors for survival (Figs 1 and 2) with significant hazard ratios for long-term
survival. The type of surgical principle (decom- pression versus resection versus hybrid procedure) and postoperative complications had no influence on long-term survival.
When considered as risk factors (1 point each), 88 patients were neither insulin dependent nor without pancreas enzyme replacement at the time
of hospital discharge (0 risk points), 53 patients were either insulin dependent or without pancreas enzyme replacement (1 risk point), and 6 patients had both risk factors for long-term survival (2 risk points). Patients with 0 versus 1 risk point at the time of hospital discharge had superior long-term survival rates (P < .001; log-rank) with 5-year Fig 1. Long-term survival of patients with versus without insulin-dependence. (A) Preoperatively. (B) Postoperatively.
survival of 85% vs 58%, respectively (Kaplan–Meier analysis). Interestingly, the dose of pancreatic enzyme replacement therapy with Kreon had no influence on 5-year mortality (P >.05, univariate regression analysis).
Postoperative quality of life. Improvement of quality of life during long-term follow-up was reported by 55 of the 76 patients who answered our questionnaire (73%). The median visual analog scale for improved quality of life was 8.0 points (range, 1–10) with 1 point representing completely absent improvement and 10 points representing an optimal improvement of quality of life. Also, 39 patients reported that they were able to achieve professional reintegration during long-term follow-up (51%). Patients who reported long-term complications were more likely to report failure of professional reintegration (P = .040; 2- sided Fisher’s exact test).
Questionnaire results on long-term postopera- tive pain control. The median visual analog scale for pain was 3.0 points (range, 0–10), with 29 patients reporting complete absence of pain (38%), 16 reporting continuous pain (21%), and 31 reporting temporary pain (41%). Chronic pain medication was used by 30 patients (40%), and 20
patients reported regular opioid use (26%). Over- all, 41 patients reported improved pain or absent pain (54%) and 11 reported identical or worse pain (15%). Patients who reported postoperative opioid treatment during follow-up (n = 20) were significantly more likely to report lack of profes- sional reintegration (n = 15), whereas patients who were free of opioid medication (n = 51) were more likely to report successful professional reintegration (n = 33; P = .003, Chi-square; P = .004, 2-sided Fisher’s exact test). Freedom from pain was more frequently reported by male pa- tients (48%) compared with female patients (22%;P= .023, 2-sided Fisher’s exact test). Patients with preoperative alcohol abuse had a greater rate of pain (P= .035, Chi-square) and were more likely to use opioids during long-term follow-up (P = .017; Fisher’s exact test).
Body weight and body mass index after long- term follow-up.The mean body weight was 70.7 kg (range, 40.0–105.0), with a mean body mass index of 23.5 kg/m2(range, 14.8–33.9). Classification of body mass index according to the current defini- tion by the World Health Organization shows an underweight classification in 6 patients (8%), normal weight in 50 (66%), a preobese Fig 2. Long-term survival of patients without versus with postoperative pancreatic enzyme substitution at the time of hospital discharge.
classification in 13 (17%), and obese class I classi- fication in 5 (7%).
Long-term postoperative endocrine function.
Diabetes mellitus was reported by 39 of 76 patients who answered our questionnaire during long-term follow-up (51%), 33 of whom (43%) were insulin- dependent. This shows an increasing incidence of insulin dependence from the preoperative phase to hospital discharge until the end of follow-up (18%, 22%, and 43%, respectively).
Long-term postoperative exocrine function.
Diarrhea was reported by 36 of 76 patients (47%) who answered our questionnaire during long-term follow-up, 39 of whom used pancreas enzyme substitution (51%); 36 patients reported food intolerance during long-term follow-up (47%).
DISCUSSION
The present study identifies significant factors for long-term survival after operative therapy for chronic pancreatitis. Long-term survival after oper- ative intervention for chronic pancreatitis has not been the main focus of previous research so far.
This study contains long-term survival data for the whole cohort with a median follow-up of 5.3 years.
This is the first study to illustrate statistically influences of preoperative insulin-dependence (Fig 1,A), postoperative insulin dependence (Fig 1,B), and postoperative pancreas enzyme replace- ment therapy at the time of hospital discharge (Fig 2) on long-term patient survival after operative treatment for chronic pancreatitis.
The data from this study demonstrate that insulin dependence at the time of hospital discharge and lack of pancreatic enzyme replace- ment therapy at the time of hospital discharge both represent significant and independent risk factors for long-term mortality after operative treatment for chronic pancreatitis with significant hazard ratios. We conclude that pancreatic enzyme replacement should be a standard treatment after operative treatment for chronic pancreatitis by the time of discharge regardless of the presence or absence of clinical signs for exocrine pancreatic failure. Furthermore, this study may underline the importance of early operative intervention in chronic pancreatitis before irreversible endocrine dysfunction is present, although our study did not address this question. Clinical studies would be desirable to determine the optimal dosing of pancreatic enzyme replacement therapy in this clinical setting.
A recent review describes the detrimental effects of pancreatic exocrine insufficiency in patients with pancreatic diseases including pancreatitis
that often result in malnutrition, weight loss, and steatorrhea, which together increase the risk of morbidity and mortality.6Currently, nutritional in- terventions including pancreatic enzyme replace- ment therapy are needed for these patients to improve clinical symptoms and to address the pathophysiology of pancreatic insufficiency.6 This treatment improves associated symptoms and the coefficients of absorption for fat, nitrogen, and lip- osoluble vitamins without serious adverse events.6 The present study highlights the value of such an approach and shows a significant impact of pancre- atic enzyme replacement therapy on long-term pa- tient survival after operative treatment of chronic pancreatitis, although a dose-dependent effect could not be verified. It may be that all patients with chronic pancreatitis may benefit from pancre- atic enzyme replacement therapy in this respect, especially in cases with subclinical exocrine pancreatic failure. Further prospective studies with functional physiologic investigations are needed to address this important issue. A compre- hensive meta-analysis came to the conclusion that the role of pancreatic enzyme replacement therapy for the treatment of abdominal pain, weight loss, steatorrhea, analgesic use, and quality of life in pa- tients with chronic pancreatitis remains equivocal,7 although Thorat et al8found recently that pancre- atic enzyme replacement therapy leads to an in- crease in weight gain. The influence of pancreatic enzyme replacement therapy on sur- vival was not evaluated so far owing to lack of pub- lished data.
Pancreatic diabetes is notoriously difficult to manage and characterized by frequent hypoglyce- mic events.1,9 Our study demonstrates the prog- nostic significance of insulin dependence before and after operative intervention for chronic pancreatitis and its influence on long-term patient survival. In this context, a large cohort study from Taiwan demonstrated that the risk of pancreatic cancer is moderately increased in patients with dia- betes, especially those using insulin therapy. Inter- estingly, the risk is greatly increased for diabetic patients with chronic pancreatitis.10This observa- tion may be relevant for patients with chronic pancreatitis suffering from insulin-dependent pancreatic diabetes. These cases may carry a greater risk of pancreatic carcinoma within morphologic changes within the pancreas that may otherwise be attributed to chronic pancrea- titis. These patients may profit from a more aggres- sive operative approach.
Some groups consider that resection for chronic pancreatitis is frequently assumed to be
more likely to result in endocrine and exocrine insufficiency and should thus be avoided in cases that could also be treated with an organ-preserving decompression procedure. This view is prevalent, although a significant negative influence of resec- tional procedures on short- or long-term endo- crine and/or exocrine pancreatic function could not be demonstrated.1,3,11,12 Our present study does not support such a notion. In this context it is interesting to note that Andersen and Frey3favor local resection or excavation of the pancreatic head, because they believe that this approach lessens the risk for early postoperative diabetes, although they were unable to demonstrate data to support this view. We believe that the operative procedures seem to be equivalent in their long- term effect as long as they are applied correctly based on the anatomic findings of the individual patient. The present study seems to underline this notion.
Our study also shows that preoperative alcohol abuse had no statistical influence on long-term survival. Alcohol abuse was the most frequent etiology for chronic pancreatitis in this cohort.
Similar observations were also described by other authors.11,13,14
The 30-day mortality was largely in line with other published series.12,15,16 In our study, the principle of operative decompression had no ef- fect on long-term survival compared with resection and hybrid principles. Other authors, however, have refuted this concept.1,17,18 In the current study, the necessity of reoperation had no influ- ence on long-term patient survival.
In our study, the surgical principle adopted (decompression versus resection versus hybrid pro- cedures) and the operative procedure itself had no influence on improvement of long-term quality of life or on the absence or improvement of pain during long-term follow-up. Aimoto et al1and van der Gaag et al12have reported recently similar obser- vations. In this context, several prospective, random- ized trials that compared 2 different operative approaches to chronic pancreatitis were unable to demonstrate statistically significant advantages of 1 method over the other in respect to clinical outcome, including quality of life, morbidity, recur- rent pain, diabetes, exocrine pancreatic function, and mortality.1,3,11,14-16,18-23In our opinion, the com- bination of morphologic changes within the pancreas and their anatomic location dictate the operative principle and the operative procedure.
This view is shared by several other authors.1,12,14,24 The results of an older, large, retrospective analysis including 504 patients with excellent
long-term follow-up (maximum, 14 years; 1972–
1998) from Germany reported improvement of quality of life for 72% of patients,15which is in line with ours, although professional reintegration was somewhat less in the current cohort. This latter observation may be influenced to some degree by societal changes in Germany within the last 40 years. A recent study from The Netherlands found that full professional reintegration with paid work could only be achieved by 34% of patients during long-term follow-up.12 The frequency of full pro- fessional reintegration during follow-up varies greatly in different publications, from 25% to 80%.11-13,15,16,20-22We believe that this variation is likely influenced by the age of the analyzed pa- tients, different durations of follow-up, and na- tional differences in social systems with different attitudes toward definitions of disability among young, chronically ill patients. Our data failed to demonstrate a significant influence of any specific operative approaches on long-term professional rehabilitation.11-13,15,16,20-22 Patients who reported postoperative opioid use during follow-up were significantly more likely to report lack of profes- sional reintegration.
Preoperative amylase and lipase levels were of no use in predicting postoperative pain control at the time of hospital discharge or during long-term follow-up.25,26Successful long-term pain control in this series could not be attributed to a specific sur- gical principle or a specific operative procedure as reported in previous publications.11-13,15,16,20-22,27
Interestingly, the present study shows that male patients achieved better long-term freedom from pain than females, in line with the greater pain prevalence in women, which is consistently observed but not well understood.28
Illegal (eg, psychostimulants, opioids, cannabi- noids) and legal (alcohol, nicotine) drugs of abuse create a complex behavioral pattern composed of drug intake, withdrawal, seeking, and relapse.29 This concept may explain our findings that pa- tients with preoperative alcohol abuse had a greater rate of subjective pain during long-term follow-up and were more likely to use opioids dur- ing long-term follow-up.
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Die Chronische Pankreatitis ist eine progressive, gutartige und schmerzhafte Entzündung des Pankreas bei der, das sekretorische Gewebe verloren geht und durch fibröses Gewebe ersetzt wird, was zum Verlust der endokrinen und exokrinen Funktion führt
1-3.
Der Schmerz in Form von wiederkehrenden Anfällen bei Pankreatitisschüben oder konstant mit lähmenden Schmerzen ist in der Regel das Hauptsymptom
1-3. Diese unerträglichen nicht mehr in den Griff zu bekommenden Schmerzen sind die häufigste Indikation, die zur Operation führen
1-3. Die wichtigsten Ziele der Operation der chronischen Pankreatitis sind, die Schmerzen zu lindern und die Funktion der Bauchspeicheldrüse zu bewahren
1-3. Diese beiden Ziele können in Fällen, die mit einer Pankreasresektion behandelt werden, auch widersprüchlich sein. Chirurgische Verfahren haben aber das Potenzial im Vergeich zu nicht-chirurgischen Behandlungen langfristige Schmerzlinderung und gute postoperative Lebensqualität zusammen mit niedrigeren Raten von Mortalität und Morbidität zu gewähren
1. Die Wahl der Therapie und der chirurgischen Strategie können in einigen Fällen schwierig sein
4, 5. Mehrere Studien haben gezeigt, dass eine lokale Pankreaskopfresektion mit oder ohne Drainage und eine duodenumerhaltende Pankreaskopfresektion ebenso effektive Ergebnisse wie eine Pankreatikoduodenektomie bieten, jedoch mit geringerer Morbidität und Mortalität
3. Die 30-Tage-Mortalität war im untersuchten Kollektiv weitgehend im Einklang mit anderen publizierten Studien
12, 15, 16. In dieser Studie zeigte sich, dass das chirurgische Verfahren der Dekompression grundsätzlich eine bessere Tendenz des langfristigen Überlebens hat im Vergleich zu den Resektions- und Hybridverfahren ohne jedoch hierbei einen statistisch signifikanten Vorteil zu erreichen. Andere Autoren beobachteten dieses ebenfalls
1, 17, 18.
Das untersuchte Patientenkollektiv bestand aus 147 Patienten (97 Männer und 50 Frauen mit einem mittleren Alter von 50,5 Jahren (Median 51 Jahre, Bereich: 22-79 Jahre), die aufgrund einer chronischen Pankreatitis in der Medizinischen Hochschule Hannover im Zeitraum zwischen dem 01.01.2000 und 31.12.2010 operiert wurden.
Der therapeutische Erfolg wurde definiert als Überleben kombiniert mit einer langfristigen Verbesserung des Hauptsymptoms Schmerz. Dies konnten wir durch einen Follow-Up-Fragebogen der operierten Patienten und in Zusammenarbeit mit den Einwohnermeldeämtern ermitteln. Das Durchschnittsnachbearbeitungsintervall lag bei 5,3 Jahren und war bei allen drei chirurgischen Prinzipien vergleichbar lang (p=0.442, two-sided Chi
2test).
Die Erfahrung mit der Operation der chronischen Pankreatitis wurde retrospektiv mit dem Ziel untersucht, noch unbekannte Faktoren für das langfristige Überleben und die Lebensqualität der Patienten zu definieren und zu prüfen, ob eine der drei chirurgischen Operationsprinzipien (Dekompression, Resektion oder Hybridverfahren) im Vergleich zu den anderen mehr Vor- oder Nachteile bietet und Faktoren detektieren, die das Langzeitüberleben signifikant beeinflussen. Das verspätete Auftreten von wiederkehrenden Schmerzen, Diabetes mellitus und der exokrinen Insuffizienz wird in der Literatur für alle drei chirurgischen Prinzipien berichtet
1-3.
1
Operationsverfahren gewählt wurde.
Einige Autoren sind der Ansicht, dass die Resektionsverfahren zur Behandlung der chronischen Pankreatitis häufiger zu einer endokrinen und exokrinen Pankreasinsuffizienz führen. Daher sollten diese Verfahren in Fällen, die auch mit einer organerhaltenden Dekompression behandelt werden könnten, möglichst vermieden werden. Diese Ansicht ist weit verbreitet, obwohl ein signifikanter negativer Einfluss der Resektionsverfahren auf die kurzfristige und langfristige endokrine und / oder exokrine Pankreasfunktion nicht gezeigt werden konnte
1, 3, 11, 12. Die Daten der vorliegenden Studie unterstützen diese Ansicht nicht. In diesem Zusammenhang ist es interessant zu erwähnen, dass Andersen und Frey eine lokale und isolierte Resektion des Pankreaskopfes favorisieren, denn sie glauben, dass dieser Ansatz das Risiko für einen pankreopriven Diabetes mellitus senkt, obwohl sie nicht in der Lage sind, Daten vorzustellen, die diese Ansicht unterstützen
3. Wir glauben auf der Basis der Ergebnisse der vorliegenden Untersuchung, dass die chirurgischen Operationsprinzipien in ihrer langfristigen Wirkung gleichwertig sind, solange sie richtig und an den pathomorphologischen Befunden und deren genauer anatomischen Lokalisation orientiert angewendet werden.
Die vorliegende Arbeit stellt fest, dass die chirurgischen Operationsprinzipien (Dekompression versus Resektion versus Hybridverfahren) und die chirurgischen Eingriffe im Detail keinen statistisch signifikanten Einfluss auf die Verbesserung der langfristigen Lebensqualität oder auf die Abwesenheit oder Verbesserung der Schmerzen während des Langzeit-Follow-Ups hatten. Aimoto et al.
1und van der Gaag et al.
12haben vor kurzem über ähnliche Beobachtungen berichtet.
Interessanterweise erwähnen mehrere prospektive randomisierte Studien, die zwei verschiedene Operationsverfahren zur chronischen Pankreatitis miteinander verglichen haben, ebenfalls keine statistisch signifikanten Vorteile des einen chirurgischen Operationsverfahrens gegenüber dem jeweils anderen In Bezug auf die klinischen Ergebnisse inklusive Lebensqualität, Morbidität, wiederkehrende Schmerzen, Diabetes mellitus, exokrine Pankreasfunktion und Mortalität
1, 3, 11, 14, 15, 16,18, 23
