Surgical Treatment of Pain in Patients with Chronic Pancreatitis

Transcription

1 PANCREAS Surgical Treatment of Pain in Patients with Chronic Pancreatitis Alexander Victorovich Prochorov 1, Karl-Jurgen Oldhafer 2, Stanislaw Ivanovich Tretyak 3, Siarhei Markovich Rashchynski 3,4, Marcello Donati 5, Nina Timofeevna Rashchynskaya 4 and Dzmitry Anatolyevich Audzevich 4 1 Department of Oncology and 3 Department of Surgery, Belarusian State Medical University, City Clinical Oncological Hospital, Minsk, Belarus 2 Department of General, Abdominal and Thorax surgery of General Hospital Celle, Academic Hospital of Medicine School, Hannover, Germany 4 Department of Hepatobiliary Surgery of the Clinic Emergency Care, Minsk, Belarus 5 Department of Surgical Sciences, Organ Transplantations and New technologies, O.U. General and Week Surgery, University Hospital of Catania, Italy Corresponding author: Alexander V. Prochorov, Nezavisimosti Av. 64, 2013, Minsk, Belarus; Tel.: , Fax: ; prochorov@tut.by 12 Οriginal Paper ABSTRACT Background/Aims: The objectives of the research were to compare the outcomes of pancreatoduodenectomy () (Kausch-Whipple or Traverso-Longmire) and resection with drainage s () (Frey or Partingtone-Rochelle) in patients suffering from chronic pancreatitis (CP), in management of pain syndrome and quality of life provided by these kinds of surgical procedures. Methodology: From 02 to 08 sixteen patients suffering from CP underwent and 16 underwent. Treatment results for the two groups were analyzed with respect to postoperative complications and results of the questionnaire MOS SF-36 v.2 тм. Results: In the immediate postoperative period more Hepato-Gastroenterology 12; 59: doi 10.54/hge10218 H.G.E. Update Medical Publishing S.A., Athens complications were observed in the group (α<0.05). In both groups a positive effect on removing the painful syndrome and improvement of the quality of life (p) were observed. In the group there were the best results of management by General Health difference criterion (α). A greater improvement of Functiong value (α) was noticed in patients who underwent. Conclusions: Both and adequately remove pain syndrome and improve the quality of life in patients suffering from CP. Under equal conditions the preference should be given to, as improvement in life quality of operated patients is greater. INTRODUCTION Today chronic pancreatitis (CP) is defined as an inflammatory process which results in progressive and irreversible pancreas exocrine and endocrine cell destruction followed by replacement by fibrous tissue (1,2). Patients ask for medical help because pain is the main clinical symptom of CP. Pain syndrome of various degrees and persistence presents in 90% of patients suffering from CP (3). Primary absence of pain in patients suffering from CP is observed in 7-10% of patients with alcohol-induced CP and in 50% of patients with idiopathic ( late-onset ) CP, who have typical clinical symptoms of the third stage of CP ( burn-out pancreas) (4). However, a painfree form of the disease still remains an exception. The dietary recommendations in combination with an adequate dose of analgesics and substitutive therapy with enzyme administration give positive effects on pain syndrome relief in more than a half of patients with CP (5). At the same time intractable pain syndrome remains the main indication for surgical treatment in 30-50% of patients suffering from CP (3,6,7). The origin of pain in patients with CP is not completely understood and it is caused by multi-factorial reasons (8). Pressure increase in pancreatic ducts and/or inside the parenchyma of the pancreas (9,10) (the so-called compartment syndrome ) plays a significant role in pain generation in patients with CP. Due to it, adequately performed resection with drainage () results to the removal of pain syndrome in -90% of patients with CP, which improves these patients quality of life (7,10). Another factor in pain generation is the presence of neuroimmunological inflammation realized through pain neurotransmitters that take part in the inflammatory reaction in patients with CP (11). Pain genesis is explained by neuroimmune inflammation in cases of CP when the head of the pancreas is enlarged without main pancreatic duct dilatation. Without proximal resection of the pancreas head it is usually impossible to drain the whole pancreatic duct that is more often stenosed in the area where it joins the duodenum. The resection of the pancreas head arrests inflammation and manages pain in 80-90% of the patients who are surgically treated (12,13). We believe that everything stated above shows expediency of surgical treatment of patients with CP. At the same time, the choice of the operative technique depends on the peculiarities of clinical manifestations of CP and must be individual. The most relevant fact is that provides the maximum relief of pain, can be used for management of other complications of CP and also, as much as possible, preserves the functional ability of pancreatic tissue. The aim of the research was to compare pancreatodu- Key Words: Chronic pancreatitis; Surgery; Pain; Quality of life. Abbreviations: Pancreatoduodenectomy (); Resection With Drainage Operations (); Chronic Pancreatitis (CP); Medical Outcomes Study 36 - Item Short-Form Health Survey (MOS SF-36 v.2 тм ); Longitudinal Pancreaticojejunostomy or Partington- Rochelle s procedure (LPJ); Local Resection of the anterior surface of the pancreas head followed by Longitudinal Pancreaticojejunostomy or Frey procedure (LR-LPJ); Traverso-Longmire Procedure (PP); Kausch-Whipple Procedure (G); Health (PH); Mental Health (MH).

2 1266 Hepato-Gastroenterology 59 (12) AV Prochorov, KJ Oldhafer, SI Tretyak, et al. odenectomy outcomes ( - Kausch-Whipple or Traverso-Longmire) and - (Frey or Partingtone-Rochelle) in patients with CP with regards to efficiency of pain syndrome relief and quality of life provided by these kinds of surgical procedures. Clinical characteristics G PP LPJ LR-LPJ Number of patients Gender (m/f) 6/0 10/0 9/2 5/0 Age (years, Ме (%-%))* 43 (41-51) 34.5 ( ) Etiology (ethyl alcohol) Pain (n) Time since onset of symptoms (mo, Ме (%-%))* 32.8 ( ,0) 29.0 ( ) Inflammatory mass in the pancreatic head (n) Pseudocysts (n) TABLE 1. Clinical characteristics of the study population. Pseudo-aneurysm of the pancreas (n) мм=2 мм=3 мм=3 мм=9 1 мм=5 мм= Common bile duct stenosis (n) Segmental duodenal stenosis (n) Segmental portal hypertension (n) Loss of body weight (>10%, n) Ductal morphology Stage IV=2 Stage IV=9 Stage IV=9 Stage IV=3 (Cambridge classification; see ref.14) Stage V=4 Stage V=1 Stage V=2 Stage V=2 Inability to work (>1 yr) (n) : Kausch-Whipple procedure or Traverso-Longmire procedure; : Partington- Rochelle procedure or Frey procedure; G: Kausch-Whipple procedure; PP: Traverso-Longmire procedure; LPJ: Partington-Rochelle procedure; LR-LPJ: Frey procedure; *α<0.05: Mann-Whitney s U-test; Ме (%-%): Median ( th percentile - th percentile). TABLE 2. Postoperative complications. Postoperative complications (n=16) (n=16) G PP LPJ LR-LPJ Wound infection (n) Pancreatic fistula (n) Inconsistency hepaticojejunostomy (n) Delayed gastric emptying (n) Relaparotomy (n) Cardiopulmonary failure (death - n) Total (n/percentage) * 6 / 37.5% 2 / 12.5% : Kausch-Whipple procedure or Traverso-Longmire procedure; : Partington- Rochelle procedure or Frey procedure; G: Kausch-Whipple procedure; PP: Traverso-Longmire procedure; LPJ: Partington-Rochelle procedure; LR-LPJ: Frey procedure; *some patients had more than one complication. METHODOLOGY From 02 to 08 in the Department of Hepatobiliary Surgery in the City Clinical Hospital of Emergency Care, (Minsk, Republic of Belarus) 466 patients with various complicated forms of CP underwent surgery. The following criteria were used to include the patients in the study groups: recurrent attacks of pain, which required analgesics within the previous 6 months; inflammatory enlargement of the pancreas head over 35mm; calcification of the pancreas parenchyma in the damaged area with (or without) stones in the pancreatic duct system; complications of CP in adjacent organs (stenosis of the distal part of the common bile duct, stenosis of the duodenum). Disease-related exclusion criteria from the study group were the following: clinical presentation of disease not associated with the enlargement of the head of the pancreas more 35mm and small duct disease (maximum diameter of the main pancreatic duct, 4-5mm); pseudocysts without duct pathology; presence of morphologically confirmed malignant damage to the pancreas; coexisting presence of histological verification of malignant tumors of other organs and isolated thrombosis of the portal vein associated with CP (Table 1). There was no significant difference between the two groups with regards to distribution of pathological findings. Two types of were used: Partington-Rochelle s procedure (LPJ) (15) with modification of pancreaticojejunostomy according to Harrison-Prinz (16) or local resection of the anterior surface of the pancreas head followed by longitudinal pancreaticojejunostomy according to Frey et al. (LR-LPJ) (17). Among the operative procedures based on the principles of resection - proximal resection of the pancreas head was used, which was performed in the form of gastropancreatoduodenal resection (G - Kausch-Whipple procedure) (18) as well as pylorus-preserving pancreatoduodenal resection (PP - Traverso-Longmire procedure) (19). During the reconstructive stage of G and PP, one-loop principle according to Child () with application of gastrojejunoanastomosis or pylorojejunoanastomosis above the area of conduction of the jejunal loop through the root of the transverse colon was used. The first group included 16 patients who had undergone pancreatoduodenal resection (G - 6, PP - 10). All 16 patients were male. The other group included sixteen patients (14 males; 2 females) who had undergone procedures (LPJ - 11, LR-LPJ - 5). In both groups all patients had alcohol consumption as a main etiological factor promoting the development of CP. The median interval between symptom onset and surgical intervention was 32.8 months (range months) in the group and 29.0 months (range months) for. While choosing the method of surgical intervention we took into account the size of the head of the pancreas, presence of the stenosis of the main pancreatic duct and biliary stenosis, suspected morphological presentation of the disease, according to the Cambridge classification, stage IV-V (29), technical feasibilities to control complications arising from adjacent organs (bile duct, duodenum). Frey s in 2 cases was followed by applying supraduodenal choledochoduodenoanastomosis, when the terminal part of the common bile duct had been critically narrowed. Evaluation of the results of surgical interventions in both groups was carried out using a version of the ques-

3 Surgical Treatment of Pain in CP Hepato-Gastroenterology 59 (12) 1267 tionnaire of the quality of life in MOS SF-36 v.2 тм (Russian version) (21). The Russian version MOS SF-36 was validated by the International Centre of life quality evaluation in Saint-Petersburg (22). The questionnaire in the patient s native language gives more objective information, due to better understanding of questions by the patients. We also took into account common and summarized results of physical (PH- Health) and psychological components of health (MH-Mental Health). The results were studied using the software package Statistica 6.0 for Windows based on Wilcoxon s rank test (comparison of treatment results in groups before and after the ) and Mann-Whitney s U-test (comparison of treatment results in two groups of patients). RESULTS Early (within 30 days after the ) and late (from 6-12 months) treatment results in the two study groups were analyzed. The analysis in the early post-operative period was carried out on the basis of post-operative complications (Table 2). Comparison of the results of surgical treatment according to the Mann-Whitney s U-test (α<0.05) showed better results for surgical treatment in the group. No patients died in the hospital in the group. Mortality in the group (6.%) was caused by cardioplegia in 1 patient in the early post-operative period due to heart rhythm disturbance (myocardial infarction in anamnesis). Two patients from the group required surgical re - 1 patient after G (pancreatic fistula and wound infection) and one patient after PP (inconsistency of the hepaticojejunostomy). During one year follow-up there was no late mortality in both groups. In order to compare the results of treatment in the late post-operative period we used the results of the questionnaire of the quality of life MOS SF-36 v.2 тм in Russian version (21,22). The results of quality of life evaluation obtained in both study groups before surgical intervention and after the are shown in Table 3. There was no significant difference between G and PP with regard to pre- and postoperative values of the questionnaire on the quality of life MOS SF-36 v.2 тм in the Russian version. During comparison of the quality of life of the operated patients the improvement in the quality of life was seen in all the values (Table 3), both in the group of patients (p), and in the group where surgical procedures were managed by principles (p). The data obtained confirm appropriateness and efficiency of surgical treatment in patients with complicated forms of CP. To compare the quality of life of patients in vs. groups the analysis the Mann-Whitney U-test before and after surgical intervention was performed (Table 4). Before the surgical s (Table 4) the lower indices of physical functioning (α) and physical health (α<0.05) in the group were recorded, which indicate a more marked degree of the patients limited physical activity due to their health condition. A higher index of health condition and prospective results of treatment after the surgical procedure were noted by the patients of the group (general health (α<0.05)). In order to assess the influence of various types of s ( vs. ) on the increase in the quality of life, indices (Mann-Whitney U-test) were compared in both study groups of patients (Table 5). In the functiong (n=15) (Ме (%-%)) Before Role-physical 0 (0-0) Bodily pain 12 (0-32) General health Vitality group treatment outcome is reliably better according to the difference in general health value (α), which demonstrates a higher index of health condition and treatment prospective in patients who had under- Social functioning Roleemotional health TABLE 3. Quality of life evaluation according to MOS SF-36 v.2тм before and follow-up. (-30) (-37.5) 0 (0-0) (-40) 32.1 After (70-80) (50-) (84-) 62 (62-67) (-70) Rate p (n=16) (Ме (%-%)) Before 22.5 ( ) 0 (0-0) 17 (12-22) 30 (-35) (10-) 87.5 (-87.5) (12.5-) 66.7 (66-) 0 (0-0) (-) 46.6 ( ) 27.8 ( ) ( ) ( ) ( ).1 ( ) After Rate p 72.5 (70-) (62.5-) 92 (84-) 54.5 (52-62) (60-) 81.3 (-87.5) (66-).8 ( ) 54.6 ( ) : Kausch-Whipple procedure or Traverso-Longmire procedure; : Partington-Rochelle procedure or Frey procedure; Ме (%-%): Median ( th percentile - th percentile); p: Wilcoxon s rank test. functiong before before Rates α after Ме (%-%) Ме (%-%) 22.5 ( ) α (70-80) (50-) Role-physical 0 (0-0) 0 (0-0) Bodily pain 12 (0-32) General health Vitality Social functioning Roleemotional health TABLE 4. Comparison of quality of life evaluation according to MOS SF-36 v.2тм before and follow-up. (-30) (-37.5) 17 (12-22) 30 (-35) (10-) (12.5-) 0 (0-0) 0 (0-0) (-40) (-) (84-) 62 (62-67) (-70) 87.5 (-87.5) 66.7 (66.7-) after Rates α 0 (0-0) 12 (0-32) (-30) (-37.5) α<0.05 * 0 (0-0) (-40) ( ) ( ) α< ( ) ( ) ( ) ( ) ( ) ( ) : Kausch-Whipple procedure or Traverso-Longmire procedure; : Partington-Rochelle procedure or Frey procedure; Ме (%-%): Median ( th percentile - th percentile); α: Mann-Whitney s U-test.

4 1268 Hepato-Gastroenterology 59 (12) AV Prochorov, KJ Oldhafer, SI Tretyak, et al. TABLE 5. Comparison of increase in quality of life evaluation according to MOS SF-36 v.2тм before and follow-up. Difference Ме (%-%) Difference Ме (%-%) Rates α functiong 35 (-40) 50 ( ) α Role- (50-) (62.5-) Bodily pain 72 (62-84) 72 (62-88) General health 37 (-42) 27 (22-32) α Vitality 50 (35-60) 55 ( ) Social functioning 50 ( ) 62.5 ( ) Role-Emotional 66.7 (66.7-) (66.7-) 48 (44-56) 56 (50-68) health 15.8 ( ).6 ( ) 17.3 ( ) gone G and PP. In patients who had undergone there was a higher increase in the physical functiong value (α) which was reflected by the degree of physical and psycho-emotional condition of the study participant, which allows them to perform daily work and communicate with people. DISCUSSION According to the randomized trial data comparing the Whipple resection and the pylorus preserving modification, offers major advantages of pain control and quality of life of the patients suffering from CP (23,24-27). Extended drainage by LR-LPJ provides a better quality of life, though both procedures are equally effective in terms of pain relief and definite control of complications affecting adjacent organs (23). According to Klempa et al. (24), who compared the outcome of standard Whipple resection and duodenumpreserving pancreatic head resection (DPPHR - Beger s procedure ()) in the treatment of selected patients with CP, DPPHR has better pain relief and weight gain. DPPHR vs. PP led to a significant increase in body 30.1 ( ) : Kausch-Whipple procedure or Traverso-Longmire procedure; : Partington-Rochelle procedure or Frey procedure; Ме (%-%): Median ( th percentile - th percentile); α: Mann-Whitney s U-test. mass index, better pain relief and endocrine function (). Beger s procedure provides better results in the treatment of CP than G in terms of quality of life, pain intensity as self-assessed by the patients, nutritional status and length of hospital stay (26). Similar results were reported by Belina et al. (27) but the authors used the EORTC QLQ-C30 questionnaire (29) to estimate the quality of life, re-evaluated for patients suffering from CP. We do not have a validated version of the EORTC QLQ-C30 in Russian. Total pain score decreased significantly after surgery in both groups of patients. During the follow-up period, the general quality of life improved by 30.4% in the LR-LPJ group and by 23.2% in the /PP group. Postoperative morbidity and mortality were higher in the resection group, but the difference was not significant (27). Although, according to the results of the multi-centered research of Makowiec et al. (30), Beger s, which was advocated in Europe, did not have the above mentioned advantages in comparison with PP within long-term follow-up. Recently published research of Müller et al. (31) showed that after long-term follow-up for up to 14 years, early advantages of Beger s procedure were no longer present. The analysis of long-term outcome in a randomized clinical trial suggested that the initial advantages of Beger s over PP for CP appeared not to be sustained (31). This might be because of the natural course of the disease and remaining alcohol and tobacco consumption. CONCLUSIO In both groups of patients, both and led to a significant improvement in the quality of life and pain relief after surgery for CP. Under equal conditions, the preference should be given to, as the quality of life of the operated patients was better. Surgical approach in treatment of CP must be strictly individual and should depend on the particularities of the hepatopancreatoduodenal area anatomy, character and causes of pain, basic indices of the exocrine and endocrine secretion of the pancreas and associated pathologies. ACKNOWLEDGMENTS Preparation of this manuscript was supported by Belarusian State Medical University, Dzershinski Av. 83, Minsk, Belarus. References 1. Etemad B, Whitcomb DC: Chronic pancreatitis: diagnosis, classification and new genetic developments. Gastroenterology 01; 1: Schneider A, Lohr 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 07; 42: Lankisch PG: Natural course of chronic pancreatitis. 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