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Optimizing Surgical Therapy for Chronic Pancreatitis
Invited Review
Pancratology
Pancreatology 2002;2:379-385
Optimizing Surgical Therapy for Chronic Pancreatitis W.T. Knoefel C.F. Eisenberger T. Strate J.R. Izbicki Department of Surgery, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany
KeyWords Chronic pancreatitis· Surgery· Quality of life· Complications
Introduction
Treatment of patients suffering from complications of chronic pancreatitis remains a major challenge [1]. The most distressing symptom for the patient is pain, which in many instances has already lead to a considerable analgesics abuse before a specialist is even consulted. Current therapeutic concepts, accordingly, aim at alleviating pain and at management of organ complications. Abstaining from excessive alcohol consumption does not interrupt the process of organ destruction [2]. On the other hand, surgical intervention has its inherent risks. Endoscopic treatment may have lower risks than surgical intervention but results from randomized studies are not yet available [3]. Endoscopic treatment is consequently not compared to data available on surgical therapy in this review. Surgical treatment of chronic pancreatitis has seen its ups and downs over the past decades [4-7]. The risk of pancreatic surgery were initially high [8-12], but many surgeons were impatient enough to approach the chronically inflamed and enlarged pancreas. The pathophysiology of the disease was, and partially still is, poorly understood. An appropriate surgical procedure was therefore
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difficult to devise. The high risks, non-evidence-based procedures, poor timing, and inadequate assessment of outcome resulted in an enforced search for alternative approaches between watchful waiting and endoscopic interventions. After we have seen an improvement in reporting the outcome of treatment [13, 14], we can now benefit from these efforts and compare the results surgical evolution has produced over the last decade.
Indications for Surgical Intervention
Currently the following frequent indications for surgical intervention are generally accepted: (1) intractable pain; (2) suspicion of a malignant neoplasm; (3) nonresolving common bile duct stenosis; (4) non-resolving duodenal stenosis; (5) pseudoaneurysms or vascular erosions not controlled by radiological intervention; (6) endoscopically not controlled large pancreatic pseudocysts; (7) conservatively intractable internal pancreatic fistula. The ideal surgical approach should address all these problems. At the same time, and perhaps most importantly, the quality of life of the patient has to be improved. Since the underlying disease is a benign disorder and patients frequently present already at a young age, these operations should also preserve a maximum of endocrine and exocrine function and long-term follow-up has to prove a low relapse rate.
Wolfram Trudo Kno efel, M D Depar tmen t of Surgery, Unive r8i Uitsklini kum H am burg-Eppendorf Martinistrasse 52, D-202 46 Hamburg (Germ any) Te l. +49 40 42803 4401/44 02, Fax +49 40 428036756 E-Mail knoe [email protected]
In case a surgical procedure has to be considered, the goals to be achieved have to be clearly defined. This review will consequently evaluate surgical procedures by their ability to permanently control the above-named complications of chronic pancreatitis. At the same time the effect of surgery on quality oflife and pancreatic function will be considered.
Selecting a Procedure
Pain Control Drainage Procedures As 40-60% of patients with painful chronic pancreatitis present with ductal ectasia, decompression of the pancreatic ductal system has become one of the main therapeutic principles. This is assuming that ductal ectasia indicates intraductal hypertension [15, 16]. Obstruction of Wirsung's or Santorini's duct results from single or multiple dominant strictures of the ductal system, from obstruction of the ductal lumen by calcium carbonate stones, or by a combination of both. The operative removal of pancreatic stones was already described at the turn of the century [17, 18]. Coffey [19] and Link [20] first described the concept of decompressing the pancreatic main ducts with a bypass of the obstruction. The first clinical applications of this principle were independently performed by DuVal [21] and Zollinger [22]. However, this procedure proved to be effective only if there was a single dominant obstruction between the pancreatic tail and the ampulla of Vater. Especially in patients with alcohol abuse a single dominant stricture is rarely found. But even with a patent drainage of the duct system, recurrent bouts of severe pain are frequently observed. In 1956, Puestow and Gillesby [23] presented another drainage procedure: decompression of the main pancreatic duct was performed by a longitudinal latero-lateral pancreaticojejunostomy after resection of the pancreatic tail. A modification of the Puestow-Gillesby procedure was introduced by Partington and Rochelle [24], who performed a longitudinal pancreaticojejunostomy while preserving the spleen and pancreatic tail. This procedure became the standard drainage procedure for chronic pancreatitis. The wide-spread application of these drainage procedures in comparison to resections was based on lower morbidity and mortality in older series. Long-term follow-up of drainage operations is burdened by a significant rate of clinically relevant pain
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recurrences. Approximately one third to one half of patients do not experience permanent pain relief [7, 16,2530]. The fault in the design of this surgical strategy is that most patients present with an inflammatory tumor in the head of the pancreas and in the uncinate process, with proximal strictures of the main pancreatic duct or pancreatic ducts of second or third order. All of which are not adequately addressed by a longitudinal pancreaticojejunostomy since it was shown that parenchymal hypertension occurs frequently, correlates with pain, and is independent from main pancreatic duct pressure [31, 32]. Quality of life results have not been evaluated in a validated fashion in these, mostly older, series. Endocrine function and exocrine function, as well, were rarely assessed in a standardized prospective fashion. Large retrospective series state a minimal loss of pancreatic function [7,33]. Interestingly, two prospective studies have shown the ability of a successful drainage operation to prevent further loss of pancreatic function [34, 35]. This finding illustrates the importance to halt the inflammatory process in order to preserve pancreatic endocrine and exocrine functions. The sacrifice of some functional tissue to reach this goal may easily be justified. In summary, the occasional patient with ductal dilatation, i.e. ductal diameter> 7 mm, no inflammatory mass in the head of the pancreas, and a normal ductal system in the head and uncinate process (no small-duct disease!), is the only suitable candidate for a longitudinal pancreaticojejunostomy.
Resection Irrespective of the width of the Wirsungian duct, approximately 90-95 % of patients suffering from chronic pancreatitis that are referred to surgery present with a problem located in the head of the pancreas, i.e. proximal ductal alterations and/or the development of an inflammatory mass [36]. Consequently, the head of the pancreas has been referred to as the pacemaker of the disease and of its complications [37-41]. An inflammatory mass in the head of the pancreas is defined as a pancreatic head with a diameter larger than 35 mm. An inflammatory mass in the head of the pancreas is considered a contraindication for a 'simple' drainage procedure as described above. Without resection of parts of the pancreatic head it is usually impossible to drain the entire pancreatic duct all the way to the stenosis most proximal to the papilla. Pancreatic ducts of second or third order are never drained in a longitudinal pancreaticojejunostomy. No study has yet shown pain being only attributable to main duct obstruction, and it is difficult to think of a good reason to believe
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so. In addition, the pathogenesis of pain is most likely not only related to ductal and parenchymal hypertension, but also to parenchymal and neuronal alterations. These are the reasons to favor pancreatic resections for chronic pancreatitis. Apart from resections of the head of the pancreas, near total or total pancreatectomy and distal resections were proposed in the past. Total or near total resections have a deleterious effect on pancreatic function and an excessively high late morbidity and mortality [6]. These procedures were consequently abandoned. Treatment of only the distal pancreas frequently falls short of relieving pain [26] but frequently produces endocrine insufficiency [42]. This procedure is therefore indicated in the few cases with severe complications of the tail of the pancreas like pseudoaneurysms. The most frequently applied resection for chronic pancreatitis today is a resection of the head of the pancreas, such as partial pancreatoduodenectomy and pylorus-preserving partial pancreatoduodenectomy. In approximately one third of these patients the resection has to be combined with a lateral pancreatojejunostomy to the distal pancreas [43]. The sacrifice of otherwise not diseased organs, i.e. the distal stomach, duodenum, and common bile duct, is the major disadvantage. Even though these resections are nowadays performed with very low mortality rates, they are still burdened by higher morbidity rates and a significant loss of pancreatic exocrine and endocrine function in many studies [31, 44-49]. Only few authors found comparable results in endocrine function after partial pancreatoduodenectomy [50]. Quality of life is improved after partial pancreatoduodenectomy [45,50, 51] although duodenum-preserving resections fare even better in this parameter [45]. Long-term pain control can be achieved in up to 90% after partial pancreatoduodenectomy [43, 45, 48]. These results in achieving pain control are unmatched by any drainage operation.
Combination o/Drainage and Resection
Duodenum-preserving resection of the head of the pancreas was first introduced by Beger [52, 53]. This procedure includes subtotal resection of the pancreatic head following transection of the pancreas above the portal vein. The body and head of the pancreas are drained by two pancreatojejunostomies using a Roux-en-Y loop. The most frequently used modification leaves a rim of pancreatic tissue across the portal and superior mesenteric vein [4,54,55]. In chronic pancreatitis with an inflammatory tumor of the pancreatic head this operative step may represent the most challenging part of the operation due to displacement and/or compression of the mesentericoportal vein axis. This modification also facilitates the operation since only one continuous pancreatojejunostomy has to be performed. The amount of tissue resected is dictated by the disease but always should involve removal of the enlarged head of the pancreas. Mortality rates of these procedures range between a and 3% [4, 54, 37] in experienced centres and are comparable to those after partial pancreatoduodenectomy or pylorus-preserving pancreatoduodenectomy [50]. Several other modifications of duodenum-preserving pancreatic head resections were described [56-61]. None of these procedures, however, produced results superior to duodenum-preserving pancreatic head resection. The numbers reported were low and randomized trials are lacking. The normal diameter of the pancreatic main duct amounts to 3-5 mm dependent on age [15, 16]. In the surgical literature there is considerable controversy regarding the definition of a dilated or narrow pancreatic duct [15,62]. Normal duct size is frequently encountered in painful chronic pancreatitis. To address this 'smallduct disease' with a maximal Wirsungian duct diameter of less than 3 mm, duodenum-preserving resection was combined with a longitudinal V-shaped excision of the ventral aspect of the pancreas. Reconstruction is performed with a longitudinal pancreatojejunostomy [45]. Recurrences, requiring surgical relief, do not necessari-
In order to limit the extent of resection to the diseased tissue, extended drainage and limited resection procedures were devised as an alternative to organ-sacrificing procedures like partial pancreatoduodenectomy and pylorus-preserving partial pancreatoduodenectomy and as opposed to 'simple' drainage operations. These procedures are all duodenum-preserving resections of the pancreas, targeted primarily at the head of the pancreas. The aim of these procedures is to combine the advantages of better pancreatic function of the drainage procedures and better pain con trol of the resections.
ly result in extensive surgical procedures. Redoing the local excision of the pancreatic head usually provides satisfactory pain relief and controls complications. These combinations of extended drainage and limited resection provide long-term pain relief in 75-95% of the patients [37, 38, 45, 54, 63-66]. There is only one randomized trial comparing the original duodenum-preserving resection of the head of the pancreas to the variant that leaves the pancreas in its continuity [54]. No difference in pain relief and quality of life was found in this study. However, a significant reduction of postoperative
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morbidity was observed if the pancreas was not divided. After 6 years median follow-up, a trend towards better exocrine function (63 vs. 79% pathologic tests) and a better endocrine function (40 vs. 58% pathologic tests) was found if the pancreas was not divided. In one randomized study comparing Beger's procedure to pylorus-preserving partial pancreatoduodenectomy it was suggested that Beger's procedure was superior in terms of pain relief [40]. In contrast no significant difference in pain relief was found between duodenum-preserving resections and partial pancreatoduodenectomy or pylorus-preserving partial pancreatoduodenectomy in two other randomized trials after a longer follow-up in larger groups [46,65]. Exocrine function was adversely affected by partial pancreatoduodenectomy or pylorus-preserving partial pancreatoduodenectomy whereas duodenum-preserving resections did not deteriorate exocrine function. Endocrine function was impaired after partial pancreatoduodenectomy and almost unchanged after duodenumpreserving resection in one study [46], not influenced in both groups in another [45], and not analyzed in the third randomized trial. Most importantly a significant improvement in quality of life in comparison to pylorus-preserving partial pancreatoduodenectomy was proven for the limited resection and extended drainage procedure [65].
Ruling out a Malignant Neoplasm Differentiating a malignant mass in the head of the pancreas from an inflammatory tumor due to chronic pancreatitis is a major challenge. In patients with suspected chronic pancreatitis a malignant tumor has to be ruled out, at least at the time of operation. A reliable exclusion of malignant disease is not warranted by 'simple' drainage [67]. Since the pancreas is hard anyhow and enlarged in size the hope to detect a carcinoma by palpation is an illusion. Even in experienced centres approximately 10% of patients harbor a pancreatic carcinoma that is only diagnosed by histologic proof at the time of resection or after failure of drainage [16,54,65]. Only resection or limited resection and extended drainage will provide sufficient material to rule out malignancy [47, 54, 65, 66]. Thus, none of the patients with histological diagnosis of chronic pancreatitis after limited resection and extended drainage turned out to have a pancreatic carcinoma during follow-up [54, 65]. Tracking pancreatic carcinoma while digging out the pancreatic head might be a problem since tumor spillage can occur.
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This risk must be weighed against the benefits the procedure offers in the majority of patients without carcinoma.
Control a/Complications Associated complications of adjacent organs resulting from chronic pancreatitis, like distal common bile duct stenosis or gastric outlet obstruction due to duodenal stenosis, require additional bypass procedures or resection of the inflammatory tumor [15, 68]. Additional drainage procedures render the efforts futile to preserve the physiologic situation to a greater extent. The bile might be diverted or the gastroduodenal passage interrupted. Frequently these bypass procedures become necessary after an initial longitudinal pancreaticojejunostomy was performed [68]. With pylorus-preserving partial pancreatoduodenectomy or partial pancreatoduodenectomy additional drainge procedures are obviously unnecessary since the duodenum and distal bile duct are sacrificed anyhow. Duodenum-preserving resections can effectively combine the control of these complications while preserving the original anatomy. In cases of distal common bile duct stenosis or duodenal obstruction, extensive decompression of the bile duct and the duodenum represents an adequate management of these organ complications [38, 45, 69]. Identification of the intrapancreatic course of the distal bile duct may be facilitated by insertion of a metal probe into the common bile duct through a proximal choledochotomy [70]. The relevance of segmental portal hypertension for a patient with chronic pancreatitis is still poorly understood [71,72]. Only transection of the pancreas as in duodenum-preserving pancreatic head resection or partial pancreatoduodenectomy will truly free the portal vein and superior mesenteric vein immediately. The removal of the majority of the inflammatory tissue around these vessels and a postulated regression of inflammation might also improve blood flow. However, complications from segmental portal hypertension are extremely rare. Its presence should therefore not influence the choice of an operation. In contrast complete portal vein obstruction with cavernomatous transformation was considered as contraindication for any effective surgical procedure for chronic pancreatitis. The risk of hepatic ischemia was considered too high to perform a partial pancreatoduodenectomy. Extended drainage and limited resection procedures, in contrast, were shown to deliver control of symptoms and be safe at the same time [73].
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Complications such as internal fistula, pseudocysts, pancreaticoportal fistula, pancreatico-arterial fistula, or pseudoaneurysms require an individualized approach. Usually, customizing the extent of drainage to incorporate the origin of the fistula or the origin of the pseudocyst will suffice. Vascular communications can be occluded or, if necessary, the vessel can be reconstructed.
Conclusion
Duodenum-preserving resections of the pancreas that include the head of the pancreas provide us with the opportunity to control pain permanently with the highest rate of success that is only matched by partial pancreato-
duodenectomy. Endocrine and exocrine functions favor the organ-sparing procedures. Quality of life is also superior after duodenum-preserving resections. The variant that leaves the pancreas intact on top of the portal vein carries a lower morbidity and therefore seems preferable. This combination of limited resection and extended drainage can easily be custom tailored to the patient's particular pathology to include treatment of all complications. It combines the highest safety of all effective surgical procedures for chronic pancreatitis with the highest efficacy. It consequently might sound to be the one ideal operation for chronic pancreatitis. In fact, however, it is an operative strategy that is slightly modified for every operation to match the patient's needs.
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Invited Commentary Michael Trede Chirurgische Klinik, Klinikum Mannheim, Universitat Heidelberg, Mannheim, Deutschland
On the paper 'Optimizing Surgical Therapy for Chronic Pancreatitis' by Knoefel WT, et al. Is it necessary to comment on a review? Not really especially if the commentator finds so little to quarrel with as is the case with this excellent and balanced review. A few comments may nevertheless be in order. It befits any surgeon, when discussing the management of chronic pancreatitis, to state at the outset that this is not a surgical disease - not primarily. Following this conservative approach, four out of ten patients referred to this commentator for surgical treatment of their chronic pancreatitis were advised against any operation. (Needless to say, some of these went 'elsewhere' to have a resection anyway.) Having said this, it is quite clear that many patients (and some of their doctors) are not prepared to wait for conservative measures to take effect. And indeed, waiting may be dangerous whenever the complications of the disease or the suspicion of cancer supervene. The old controversy - resection or drainage - is now irrelevant. Both have their place and both have the same aims: to alleviate the mechanical complications and symptoms (especially pain), whilst preserving as much as possible of endocrine and exocrine pancreatic functions for as long as possible. And there are a number of operations that combine resection with drainage. In a complex and variegated disease such as chronic pancreatitis, it is small wonder that many different roads seem 'to lead to Rome'. The reviewers leave no doubt as to which path they prefer: some duodenum-preserving
resection of the head of the pancreas - preferably in the variant of Frey. However, they are fair enough to concede that this only 'might sound to be the one ideal operation', leaving us with the conclusion that other variants may match the individual patient's needs equally well. This operation indeed combines effectiveness with the principle that 'less is more', since it preserves certain organs (antrum, duodenum, choledochus), the alkaline duodenal secretions as well as the 'entero-insular-axis'. However, the results (both short- and long-term) of pancreatoduodenectomy (both Whipple or pylorus-preserving) are equally good [see Trede M: Langenbecks Arch., Chir. 372, 379 (1987)]. So good in fact, that they are still being implemented by most well-known pancreatic centers in the United States (Johns Hopkins, Mass. General Hospital, Mayo Clinic). In this commentator's view, one of the drawbacks of all methods confining themselves to partial resection of the pancreatic head concerns the ruling out of malignancy. In 131 pancreatoduodenectomies performed for chronic pancreatitis in the period between 1972 and 1998, the final histology unexpectedly showed pancreatic carcinoma in 22 cases (i.e. 17%). In a report from Erlangen this percentage was twice as high. Some of these malignant tumors might have been transected (causing tumor spillage) or missed altogether by any form of partial resection (especially when small and located close to the papilla).
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Optimizing Surgical Therapy for Chronic Pancreatitis W.T. Knoefel C.F. Eisenberger T. Strate J.R. Izbicki Department of Surgery, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany
KeyWords Chronic pancreatitis· Surgery· Quality of life· Complications
Introduction
Treatment of patients suffering from complications of chronic pancreatitis remains a major challenge [1]. The most distressing symptom for the patient is pain, which in many instances has already lead to a considerable analgesics abuse before a specialist is even consulted. Current therapeutic concepts, accordingly, aim at alleviating pain and at management of organ complications. Abstaining from excessive alcohol consumption does not interrupt the process of organ destruction [2]. On the other hand, surgical intervention has its inherent risks. Endoscopic treatment may have lower risks than surgical intervention but results from randomized studies are not yet available [3]. Endoscopic treatment is consequently not compared to data available on surgical therapy in this review. Surgical treatment of chronic pancreatitis has seen its ups and downs over the past decades [4-7]. The risk of pancreatic surgery were initially high [8-12], but many surgeons were impatient enough to approach the chronically inflamed and enlarged pancreas. The pathophysiology of the disease was, and partially still is, poorly understood. An appropriate surgical procedure was therefore
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difficult to devise. The high risks, non-evidence-based procedures, poor timing, and inadequate assessment of outcome resulted in an enforced search for alternative approaches between watchful waiting and endoscopic interventions. After we have seen an improvement in reporting the outcome of treatment [13, 14], we can now benefit from these efforts and compare the results surgical evolution has produced over the last decade.
Indications for Surgical Intervention
Currently the following frequent indications for surgical intervention are generally accepted: (1) intractable pain; (2) suspicion of a malignant neoplasm; (3) nonresolving common bile duct stenosis; (4) non-resolving duodenal stenosis; (5) pseudoaneurysms or vascular erosions not controlled by radiological intervention; (6) endoscopically not controlled large pancreatic pseudocysts; (7) conservatively intractable internal pancreatic fistula. The ideal surgical approach should address all these problems. At the same time, and perhaps most importantly, the quality of life of the patient has to be improved. Since the underlying disease is a benign disorder and patients frequently present already at a young age, these operations should also preserve a maximum of endocrine and exocrine function and long-term follow-up has to prove a low relapse rate.
Wolfram Trudo Kno efel, M D Depar tmen t of Surgery, Unive r8i Uitsklini kum H am burg-Eppendorf Martinistrasse 52, D-202 46 Hamburg (Germ any) Te l. +49 40 42803 4401/44 02, Fax +49 40 428036756 E-Mail knoe [email protected]
In case a surgical procedure has to be considered, the goals to be achieved have to be clearly defined. This review will consequently evaluate surgical procedures by their ability to permanently control the above-named complications of chronic pancreatitis. At the same time the effect of surgery on quality oflife and pancreatic function will be considered.
Selecting a Procedure
Pain Control Drainage Procedures As 40-60% of patients with painful chronic pancreatitis present with ductal ectasia, decompression of the pancreatic ductal system has become one of the main therapeutic principles. This is assuming that ductal ectasia indicates intraductal hypertension [15, 16]. Obstruction of Wirsung's or Santorini's duct results from single or multiple dominant strictures of the ductal system, from obstruction of the ductal lumen by calcium carbonate stones, or by a combination of both. The operative removal of pancreatic stones was already described at the turn of the century [17, 18]. Coffey [19] and Link [20] first described the concept of decompressing the pancreatic main ducts with a bypass of the obstruction. The first clinical applications of this principle were independently performed by DuVal [21] and Zollinger [22]. However, this procedure proved to be effective only if there was a single dominant obstruction between the pancreatic tail and the ampulla of Vater. Especially in patients with alcohol abuse a single dominant stricture is rarely found. But even with a patent drainage of the duct system, recurrent bouts of severe pain are frequently observed. In 1956, Puestow and Gillesby [23] presented another drainage procedure: decompression of the main pancreatic duct was performed by a longitudinal latero-lateral pancreaticojejunostomy after resection of the pancreatic tail. A modification of the Puestow-Gillesby procedure was introduced by Partington and Rochelle [24], who performed a longitudinal pancreaticojejunostomy while preserving the spleen and pancreatic tail. This procedure became the standard drainage procedure for chronic pancreatitis. The wide-spread application of these drainage procedures in comparison to resections was based on lower morbidity and mortality in older series. Long-term follow-up of drainage operations is burdened by a significant rate of clinically relevant pain
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recurrences. Approximately one third to one half of patients do not experience permanent pain relief [7, 16,2530]. The fault in the design of this surgical strategy is that most patients present with an inflammatory tumor in the head of the pancreas and in the uncinate process, with proximal strictures of the main pancreatic duct or pancreatic ducts of second or third order. All of which are not adequately addressed by a longitudinal pancreaticojejunostomy since it was shown that parenchymal hypertension occurs frequently, correlates with pain, and is independent from main pancreatic duct pressure [31, 32]. Quality of life results have not been evaluated in a validated fashion in these, mostly older, series. Endocrine function and exocrine function, as well, were rarely assessed in a standardized prospective fashion. Large retrospective series state a minimal loss of pancreatic function [7,33]. Interestingly, two prospective studies have shown the ability of a successful drainage operation to prevent further loss of pancreatic function [34, 35]. This finding illustrates the importance to halt the inflammatory process in order to preserve pancreatic endocrine and exocrine functions. The sacrifice of some functional tissue to reach this goal may easily be justified. In summary, the occasional patient with ductal dilatation, i.e. ductal diameter> 7 mm, no inflammatory mass in the head of the pancreas, and a normal ductal system in the head and uncinate process (no small-duct disease!), is the only suitable candidate for a longitudinal pancreaticojejunostomy.
Resection Irrespective of the width of the Wirsungian duct, approximately 90-95 % of patients suffering from chronic pancreatitis that are referred to surgery present with a problem located in the head of the pancreas, i.e. proximal ductal alterations and/or the development of an inflammatory mass [36]. Consequently, the head of the pancreas has been referred to as the pacemaker of the disease and of its complications [37-41]. An inflammatory mass in the head of the pancreas is defined as a pancreatic head with a diameter larger than 35 mm. An inflammatory mass in the head of the pancreas is considered a contraindication for a 'simple' drainage procedure as described above. Without resection of parts of the pancreatic head it is usually impossible to drain the entire pancreatic duct all the way to the stenosis most proximal to the papilla. Pancreatic ducts of second or third order are never drained in a longitudinal pancreaticojejunostomy. No study has yet shown pain being only attributable to main duct obstruction, and it is difficult to think of a good reason to believe
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so. In addition, the pathogenesis of pain is most likely not only related to ductal and parenchymal hypertension, but also to parenchymal and neuronal alterations. These are the reasons to favor pancreatic resections for chronic pancreatitis. Apart from resections of the head of the pancreas, near total or total pancreatectomy and distal resections were proposed in the past. Total or near total resections have a deleterious effect on pancreatic function and an excessively high late morbidity and mortality [6]. These procedures were consequently abandoned. Treatment of only the distal pancreas frequently falls short of relieving pain [26] but frequently produces endocrine insufficiency [42]. This procedure is therefore indicated in the few cases with severe complications of the tail of the pancreas like pseudoaneurysms. The most frequently applied resection for chronic pancreatitis today is a resection of the head of the pancreas, such as partial pancreatoduodenectomy and pylorus-preserving partial pancreatoduodenectomy. In approximately one third of these patients the resection has to be combined with a lateral pancreatojejunostomy to the distal pancreas [43]. The sacrifice of otherwise not diseased organs, i.e. the distal stomach, duodenum, and common bile duct, is the major disadvantage. Even though these resections are nowadays performed with very low mortality rates, they are still burdened by higher morbidity rates and a significant loss of pancreatic exocrine and endocrine function in many studies [31, 44-49]. Only few authors found comparable results in endocrine function after partial pancreatoduodenectomy [50]. Quality of life is improved after partial pancreatoduodenectomy [45,50, 51] although duodenum-preserving resections fare even better in this parameter [45]. Long-term pain control can be achieved in up to 90% after partial pancreatoduodenectomy [43, 45, 48]. These results in achieving pain control are unmatched by any drainage operation.
Combination o/Drainage and Resection
Duodenum-preserving resection of the head of the pancreas was first introduced by Beger [52, 53]. This procedure includes subtotal resection of the pancreatic head following transection of the pancreas above the portal vein. The body and head of the pancreas are drained by two pancreatojejunostomies using a Roux-en-Y loop. The most frequently used modification leaves a rim of pancreatic tissue across the portal and superior mesenteric vein [4,54,55]. In chronic pancreatitis with an inflammatory tumor of the pancreatic head this operative step may represent the most challenging part of the operation due to displacement and/or compression of the mesentericoportal vein axis. This modification also facilitates the operation since only one continuous pancreatojejunostomy has to be performed. The amount of tissue resected is dictated by the disease but always should involve removal of the enlarged head of the pancreas. Mortality rates of these procedures range between a and 3% [4, 54, 37] in experienced centres and are comparable to those after partial pancreatoduodenectomy or pylorus-preserving pancreatoduodenectomy [50]. Several other modifications of duodenum-preserving pancreatic head resections were described [56-61]. None of these procedures, however, produced results superior to duodenum-preserving pancreatic head resection. The numbers reported were low and randomized trials are lacking. The normal diameter of the pancreatic main duct amounts to 3-5 mm dependent on age [15, 16]. In the surgical literature there is considerable controversy regarding the definition of a dilated or narrow pancreatic duct [15,62]. Normal duct size is frequently encountered in painful chronic pancreatitis. To address this 'smallduct disease' with a maximal Wirsungian duct diameter of less than 3 mm, duodenum-preserving resection was combined with a longitudinal V-shaped excision of the ventral aspect of the pancreas. Reconstruction is performed with a longitudinal pancreatojejunostomy [45]. Recurrences, requiring surgical relief, do not necessari-
In order to limit the extent of resection to the diseased tissue, extended drainage and limited resection procedures were devised as an alternative to organ-sacrificing procedures like partial pancreatoduodenectomy and pylorus-preserving partial pancreatoduodenectomy and as opposed to 'simple' drainage operations. These procedures are all duodenum-preserving resections of the pancreas, targeted primarily at the head of the pancreas. The aim of these procedures is to combine the advantages of better pancreatic function of the drainage procedures and better pain con trol of the resections.
ly result in extensive surgical procedures. Redoing the local excision of the pancreatic head usually provides satisfactory pain relief and controls complications. These combinations of extended drainage and limited resection provide long-term pain relief in 75-95% of the patients [37, 38, 45, 54, 63-66]. There is only one randomized trial comparing the original duodenum-preserving resection of the head of the pancreas to the variant that leaves the pancreas in its continuity [54]. No difference in pain relief and quality of life was found in this study. However, a significant reduction of postoperative
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morbidity was observed if the pancreas was not divided. After 6 years median follow-up, a trend towards better exocrine function (63 vs. 79% pathologic tests) and a better endocrine function (40 vs. 58% pathologic tests) was found if the pancreas was not divided. In one randomized study comparing Beger's procedure to pylorus-preserving partial pancreatoduodenectomy it was suggested that Beger's procedure was superior in terms of pain relief [40]. In contrast no significant difference in pain relief was found between duodenum-preserving resections and partial pancreatoduodenectomy or pylorus-preserving partial pancreatoduodenectomy in two other randomized trials after a longer follow-up in larger groups [46,65]. Exocrine function was adversely affected by partial pancreatoduodenectomy or pylorus-preserving partial pancreatoduodenectomy whereas duodenum-preserving resections did not deteriorate exocrine function. Endocrine function was impaired after partial pancreatoduodenectomy and almost unchanged after duodenumpreserving resection in one study [46], not influenced in both groups in another [45], and not analyzed in the third randomized trial. Most importantly a significant improvement in quality of life in comparison to pylorus-preserving partial pancreatoduodenectomy was proven for the limited resection and extended drainage procedure [65].
Ruling out a Malignant Neoplasm Differentiating a malignant mass in the head of the pancreas from an inflammatory tumor due to chronic pancreatitis is a major challenge. In patients with suspected chronic pancreatitis a malignant tumor has to be ruled out, at least at the time of operation. A reliable exclusion of malignant disease is not warranted by 'simple' drainage [67]. Since the pancreas is hard anyhow and enlarged in size the hope to detect a carcinoma by palpation is an illusion. Even in experienced centres approximately 10% of patients harbor a pancreatic carcinoma that is only diagnosed by histologic proof at the time of resection or after failure of drainage [16,54,65]. Only resection or limited resection and extended drainage will provide sufficient material to rule out malignancy [47, 54, 65, 66]. Thus, none of the patients with histological diagnosis of chronic pancreatitis after limited resection and extended drainage turned out to have a pancreatic carcinoma during follow-up [54, 65]. Tracking pancreatic carcinoma while digging out the pancreatic head might be a problem since tumor spillage can occur.
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This risk must be weighed against the benefits the procedure offers in the majority of patients without carcinoma.
Control a/Complications Associated complications of adjacent organs resulting from chronic pancreatitis, like distal common bile duct stenosis or gastric outlet obstruction due to duodenal stenosis, require additional bypass procedures or resection of the inflammatory tumor [15, 68]. Additional drainage procedures render the efforts futile to preserve the physiologic situation to a greater extent. The bile might be diverted or the gastroduodenal passage interrupted. Frequently these bypass procedures become necessary after an initial longitudinal pancreaticojejunostomy was performed [68]. With pylorus-preserving partial pancreatoduodenectomy or partial pancreatoduodenectomy additional drainge procedures are obviously unnecessary since the duodenum and distal bile duct are sacrificed anyhow. Duodenum-preserving resections can effectively combine the control of these complications while preserving the original anatomy. In cases of distal common bile duct stenosis or duodenal obstruction, extensive decompression of the bile duct and the duodenum represents an adequate management of these organ complications [38, 45, 69]. Identification of the intrapancreatic course of the distal bile duct may be facilitated by insertion of a metal probe into the common bile duct through a proximal choledochotomy [70]. The relevance of segmental portal hypertension for a patient with chronic pancreatitis is still poorly understood [71,72]. Only transection of the pancreas as in duodenum-preserving pancreatic head resection or partial pancreatoduodenectomy will truly free the portal vein and superior mesenteric vein immediately. The removal of the majority of the inflammatory tissue around these vessels and a postulated regression of inflammation might also improve blood flow. However, complications from segmental portal hypertension are extremely rare. Its presence should therefore not influence the choice of an operation. In contrast complete portal vein obstruction with cavernomatous transformation was considered as contraindication for any effective surgical procedure for chronic pancreatitis. The risk of hepatic ischemia was considered too high to perform a partial pancreatoduodenectomy. Extended drainage and limited resection procedures, in contrast, were shown to deliver control of symptoms and be safe at the same time [73].
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Complications such as internal fistula, pseudocysts, pancreaticoportal fistula, pancreatico-arterial fistula, or pseudoaneurysms require an individualized approach. Usually, customizing the extent of drainage to incorporate the origin of the fistula or the origin of the pseudocyst will suffice. Vascular communications can be occluded or, if necessary, the vessel can be reconstructed.
Conclusion
Duodenum-preserving resections of the pancreas that include the head of the pancreas provide us with the opportunity to control pain permanently with the highest rate of success that is only matched by partial pancreato-
duodenectomy. Endocrine and exocrine functions favor the organ-sparing procedures. Quality of life is also superior after duodenum-preserving resections. The variant that leaves the pancreas intact on top of the portal vein carries a lower morbidity and therefore seems preferable. This combination of limited resection and extended drainage can easily be custom tailored to the patient's particular pathology to include treatment of all complications. It combines the highest safety of all effective surgical procedures for chronic pancreatitis with the highest efficacy. It consequently might sound to be the one ideal operation for chronic pancreatitis. In fact, however, it is an operative strategy that is slightly modified for every operation to match the patient's needs.
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Invited Commentary Michael Trede Chirurgische Klinik, Klinikum Mannheim, Universitat Heidelberg, Mannheim, Deutschland
On the paper 'Optimizing Surgical Therapy for Chronic Pancreatitis' by Knoefel WT, et al. Is it necessary to comment on a review? Not really especially if the commentator finds so little to quarrel with as is the case with this excellent and balanced review. A few comments may nevertheless be in order. It befits any surgeon, when discussing the management of chronic pancreatitis, to state at the outset that this is not a surgical disease - not primarily. Following this conservative approach, four out of ten patients referred to this commentator for surgical treatment of their chronic pancreatitis were advised against any operation. (Needless to say, some of these went 'elsewhere' to have a resection anyway.) Having said this, it is quite clear that many patients (and some of their doctors) are not prepared to wait for conservative measures to take effect. And indeed, waiting may be dangerous whenever the complications of the disease or the suspicion of cancer supervene. The old controversy - resection or drainage - is now irrelevant. Both have their place and both have the same aims: to alleviate the mechanical complications and symptoms (especially pain), whilst preserving as much as possible of endocrine and exocrine pancreatic functions for as long as possible. And there are a number of operations that combine resection with drainage. In a complex and variegated disease such as chronic pancreatitis, it is small wonder that many different roads seem 'to lead to Rome'. The reviewers leave no doubt as to which path they prefer: some duodenum-preserving
resection of the head of the pancreas - preferably in the variant of Frey. However, they are fair enough to concede that this only 'might sound to be the one ideal operation', leaving us with the conclusion that other variants may match the individual patient's needs equally well. This operation indeed combines effectiveness with the principle that 'less is more', since it preserves certain organs (antrum, duodenum, choledochus), the alkaline duodenal secretions as well as the 'entero-insular-axis'. However, the results (both short- and long-term) of pancreatoduodenectomy (both Whipple or pylorus-preserving) are equally good [see Trede M: Langenbecks Arch., Chir. 372, 379 (1987)]. So good in fact, that they are still being implemented by most well-known pancreatic centers in the United States (Johns Hopkins, Mass. General Hospital, Mayo Clinic). In this commentator's view, one of the drawbacks of all methods confining themselves to partial resection of the pancreatic head concerns the ruling out of malignancy. In 131 pancreatoduodenectomies performed for chronic pancreatitis in the period between 1972 and 1998, the final histology unexpectedly showed pancreatic carcinoma in 22 cases (i.e. 17%). In a report from Erlangen this percentage was twice as high. Some of these malignant tumors might have been transected (causing tumor spillage) or missed altogether by any form of partial resection (especially when small and located close to the papilla).
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