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CHRONIC PANCREATITIS - New Pathophysiological Aspects andOrgan Preserving Surgery

 Shailesh V Shrikhande*, Helmut Friess, Marcus E Martignoni, Pascal Orberat, Arkus W Buchler
*Financial Assistance from RD Birla Smark Kosh, Bombay Hospital Trust, Dept. of Visceral and Transplantation Surgery, University of Bern, Inselspital, CH 3010 Bern, Switzerland
ABSTRACT
Treatment of chronic pancreatitis (CP) is often a matter of controversial discussion between surgeons and gastroenterologists. Surgical techniques have gradually improved with reduced perioperative morbidity and mortality over the years while the conservative treatment leaves a lot to be desired. This has been mainly due to the fact that the underlying pathophysiological mechanisms which are responsible for the morphological and functional alterations of chronic pancretitis have largely remained unclear.

In this review article, with the advent of modern molecular biology techniques, some new pathophysiological aspects of CP have evolved and they are discussed. The mechanisms involved in the generation of pain — one of the dominant features of chronic pancreatitis — are dealt with in detail. Also, the fibrosis which replaces the pancreatic parenchyma ultimately leading to maldigestion, is discussed at the basic science level. We believe this newly acquired knowledge could lead to novel treatment strategies in the management of chronic pancreatitis in the future.

Lastly, refinements in the various surgical techniques adopted for chronic pancreatitis, their strengths and weaknesses, are elucidated and discussed. In addition, data of prospective randomised clinical trials are presented indicating that duodenum-preserving pancreatic head resections should replace the Whipple resection as surgical standard in head-related complications in CP.

 

INTRODUCTION

Chronic pancreatitis (CP) is an inflammatory disease of the pancreas which leads to persistent and progressive morphological and functional alterations of the whole organ. In the terminal state of the disease the extended fibrosis leads to exocrine and endocrine pancreatic insufficiencies. [1-3] Histomorphologically, the chronic inflammation of the pancreas is often characterized by pancreatic head enlargement, calcifications, pseudocyst formation, fibrosis and atrophy. [4-6] The leading clinical symptoms in chronic pancreatitis are upper abdominal pain and maldigestion. In the following review, we will describe some new pathophysiological aspects which have evolved in recent years in the understanding of this confounding disease and we will compare different surgical treatment options which are currently followed in chronic pancreatitis.

Pain - a leading symptom in chronic pancreatitis

Although many studies have attempted to clarify the pathobiological mechanisms of pain generation in chronic pancreatitis, all proposed hypotheses are still controversial. Theories of pain pathogenesis have included focal acute inflammation of the pancreas, increased intraductal and or parenchymal pressure, extrapancreatic causes like common bile duct stenosis or duodenal stenosis, and postprandial pancreatic hyperstimulation due to the decreased secretion capacity and the insufficient functioning of the so-called "negative feed

back mechanism". [7,8] However, none of these concepts can explain the pain syndrome in CP patients conclusively. Recent studies using modern molecular biology techniques such as Northern blot analysis, in situ hybridization and immunostaining have led to the postulation that direct alterations of nerves and changes in neurotransmitters might cause pain in patients with chronic pancreatitis. [9-11] Furthermore, a significantly greater diameter and density of nerves in combination with the destruction of the perineurium have been described in chronic pancreatitis in comparison with the normal pancreas. In addition to these morphological alterations, increased levels of growth-associated protein 43 (GAP-43) and of the pain-transmitting neuropeptides ‘substance P’ (SP) and ‘calcitonin-gene-related peptide’ (CGRP) are present in intrinsic neurons and nerve fibres in chronic pancreatitis.[9,11] All these findings suggest that nerves in chronic pancreatitis are actively growing and that a combination of neural alterations play a significant role in pain generation in these patients.

Thus, there is great expectation that the further development of new molecular methods will help to complete our understanding of pain generation in chronic pancreatitis in the coming years.

Pathophysiological aspects of chronic pancreatitis

The second leading symptom of patients with chronic pancreatitis is maldigestion, which is generally caused by the loss of exocrine parenchyma. However, the mechanisms which lead to the destruction of the exocrine pancreas and the replacement of pancreatic acinar and ductal cells by fibrosis are not known. In the past, several independent pathophysiological concepts of chronic pancreatitis were introduced by different research groups, but there is still disagreement over which one of them gives the most valid explanation for the morphological changes which occur in chronic pancreatitis. [12-15] The most favoured concept postulates that alcohol over consumption leads to a reduction in the secretion of lithostatin, a protein which stabilizes the pancreatic juice and inhibits the formation of protein plugs; it is believed that protein plugs are formed due to reduced lithostatin secretion which then leads to obstruction of the pancreatic ductal system and subsequently to a chronic inflammatory reaction in the pancreas.[12] Other proposed causes include recurrent attacks of acute pancreatitis with subsequent small parenchymal necrosis and later periductular fibrosis; ductal obstruction and continuous fibrosis; [13] the direct toxic effect of alcohol and its metabolites on pancreatic acinar and ductal cells, [14] and direct damage of the pancreatic parenchyma by increased levels of free radicals caused by reduced hepatic detoxification. [15] However, none of these concepts could explain the morphological, functional and clinical picture of chronic pancreatitis conclusively. [16] Therefore, additional mechanisms must be involved in the pathogenesis of chronic pancreatitis. We favour a new hypothesis of inflammatory destruction which causes pain and exocrine/endocrine failure. Recently, we have reported that there exists a correlation between inflammatory cell infiltrates, pain and changes in and around pancreatic nerves. [17] Exocrine and endocrine pancreatic destruction and fibrotic replacement seems to be additionally influenced by activated lymphocytes and by activation of non-pancreatic proteolytic systems. [18,19]

Molecular biology techniques have enabled clinicians to gain deeper insight into the pathophysiology of human diseases in the past decade. However, the molecular mechanisms which contribute to the histomorphological changes in chronic pancreatitis are still not known. Bockman and coworkers reported in 1992 that transgenic mice which overexpress transforming growth factor alpha (TGF-alpha) in the pancreas develop morphological pancreatic changes which are comparable with those found in chronic pancreatitis in humans except that the inflammatory reaction was missing. The pancreas of these transgenic mice were macroscopically firm and enlarged. [20] Microscopically, there was a high degree of fibrosis and redifferentiation of pancreatic acinar cells into tubular structures. These findings provided the first hint that growth factors and growth factor receptors may play a role in the morphological changes which occur in chronic pancreatitis. We have tried to determine over the past six years whether alterations in the expression pattern of growth factors and growth factor receptors occur in chronic pancreatitis. [21-28] To name a few, epidermal growth factor receptor (EGF), transforming growth factor alpha, phospholipase C gamma, cripto, acidic and basic fibroblast growth factors and transforming growth factor betas are all increased in chronic pancreatitis. These factors are produced in the remaining pancreatic acinar and ductal cells suggesting that the exocrine pancreas itself is actively contributing to the morphological changes. Immunohistochemistry showed that areas with a higher degree of pancreatic damage exhibited the strongest staining for these factors. Thus these factors seem to influence the morphological and clinical course of this confounding disease.

Treatment options in chronic pancreatitis

The therapy for chronic pancreatitis consists primarily of conservative and symptom-related treatment. However, long-term follow-up studies have demonstrated that ultimately, about 50% of all CP patients will undergo surgical treatment at some time point in the course of the disease. [29] Surgical intervention is mandated if pain no longer responds to analgesics or if complications in the adjacent organs occur, such as common bile duct obstruction, pancreatic duct obstruction, duodenal obstruction, or major vascular involvement. [30-31] Additionally, the exclusion of pancreatic cancer is sometimes not possible even with all the available diagnostic procedures, and only surgical resection can provide a definite answer. Recently, some studies have shown that surgery can also have a positive influence on the further course of the disease, postponing the final "burn-out" of the pancreas and the consequent appearance of exocrine and endocrine insufficiency. [32] Therefore, it is of great clinical importance in the treatment of chronic pancreatitis to address the above-mentioned problems surgically before the disease has progressed to an advanced stage in which exocrine and endocrine function is completely lost.

Surgery in chronic pancreatitis : Indications

Surgical treatment of chronic pancreatitis depends on the localization and the pathomorphological appearance of complicating lesions. However, there is still controversy over which procedure to choose as the surgical standard in this field.

Surgical treatment of chronic pancreatitis can basically be divided into drainage procedures and section procedures. With regard to the preservation of exocrine and endocrine pancreatic function, drainage operations should be considered first. However, there are only a few indications for drainage procedures in chronic pancreatitis which can lead to good long-term results. If drainage procedures are used without strong indications, the long-term results are poor.

The second option to treat CP is resection. The classical Whipple resection was the standard operation in chronic pancreatitis for several decades. [33] However, in the last two decades, the classical Whipple resection has been steadily replaced by organ-preserving surgical procedures, such as the pylorus-preserving Whipple resection and the duodenum-preserving pancreatic head resection. [4,30,34-37] In the following pages we will give an overview of the surgical techniques most frequently used in the treatment of chronic pancreatitis. Nevertheless, in our opinion the duodenum-preserving pancreatic head resection is the treatment of choice to treat patients with pancreatic head-related complications. creatitis in humans except that the inflammatory reaction was missing. The pancreas of these transgenic mice were macroscopically firm and enlarged. [20] Microscopically, there was a high degree of fibrosis and redifferentiation of pancreatic acinar cells into tubular structures. These findings provided the first hint that growth factors and growth factor receptors may play a role in the morphological changes which occur in chronic pancreatitis. We have tried to determine over the past six years whether alterations in the expression pattern of growth factors and growth factor receptors occur in chronic pancreatitis. [21-28] To name a few, epidermal growth factor receptor (EGF), transforming growth factor alpha, phospholipase C gamma, cripto, acidic and basic fibroblast growth factors and transforming growth factor betas are all increased in chronic pancreatitis. These factors are produced in the remaining pancreatic acinar and ductal cells suggesting that the exocrine pancreas itself is actively contributing to the morphological changes. Immunohistochemistry showed that areas with a higher degree of pancreatic damage exhibited the strongest staining for these factors. Thus these factors seem to influence the morphological and clinical course of this confounding disease.

Treatment options in chronic pancreatitis

The therapy for chronic pancreatitis consists primarily of conservative and symptom-related treatment. However, long-term follow-up studies have demonstrated that ultimately, about 50% of all CP patients will undergo surgical treatment at some time point in the course of the disease. [29] Surgical intervention is mandated if pain no longer responds to analgesics or if complications in the adjacent organs occur, such as common bile duct obstruction, pancreatic duct obstruction, duodenal obstruction, or major vascular involvement. [30-31] Additionally, the exclusion of pancreatic cancer is sometimes not possible even with all the available diagnostic procedures, and only surgical resection can provide a definite answer. Recently, some studies have shown that surgery can also have a positive influence on the further course of the disease, postponing the final "burn-out" of the pancreas and the consequent appearance of exocrine and endocrine insufficiency. [32] Therefore, it is of great clinical importance in the treatment of chronic pancreatitis to address the above-mentioned problems surgically before the disease has progressed to an advanced stage in which exocrine and endocrine function is completely lost.

Surgery in chronic pancreatitis : Indications

Surgical treatment of chronic pancreatitis depends on the localization and the pathomorphological appearance of complicating lesions. However, there is still controversy over which procedure to choose as the surgical standard in this field.

Surgical treatment of chronic pancreatitis can basically be divided into drainage procedures and section procedures. With regard to the preservation of exocrine and endocrine pancreatic function, drainage operations should be considered first. However, there are only a few indications for drainage procedures in chronic pancreatitis which can lead to good long-term results. If drainage procedures are used without strong indications, the long-term results are poor.

The second option to treat CP is resection. The classical Whipple resection was the standard operation in chronic pancreatitis for several decades. [33] However, in the last two decades, the classical Whipple resection has been steadily replaced by organ-preserving surgical procedures, such as the pylorus-preserving Whipple resection and the duodenum-preserving pancreatic head resection. [4,30,34-37] In the following pages we will give an overview of the surgical techniques most frequently used in the treatment of chronic pancreatitis. Nevertheless, in our opinion the duodenum-preserving pancreatic head resection is the treatment of choice to treat patients with pancreatic head-related complications. creatitis in humans except that the inflammatory reaction was missing. The pancreas of these transgenic mice were macroscopically firm and enlarged. [20] Microscopically, there was a high degree of fibrosis and redifferentiation of pancreatic acinar cells into tubular structures. These findings provided the first hint that growth factors and growth factor receptors may play a role in the morphological changes which occur in chronic pancreatitis. We have tried to determine over the past six years whether alterations in the expression pattern of growth factors and growth factor receptors occur in chronic pancreatitis. [21-28] To name a few, epidermal growth factor receptor (EGF), transforming growth factor alpha, phospholipase C gamma, cripto, acidic and basic fibroblast growth factors and transforming growth factor betas are all increased in chronic pancreatitis. These factors are produced in the remaining pancreatic acinar and ductal cells suggesting that the exocrine pancreas itself is actively contributing to the morphological changes. Immunohistochemistry showed that areas with a higher degree of pancreatic damage exhibited the strongest staining for these factors. Thus these factors seem to influence the morphological and clinical course of this confounding disease.

Treatment options in chronic pancreatitis

The therapy for chronic pancreatitis consists primarily of conservative and symptom-related treatment. However, long-term follow-up studies have demonstrated that ultimately, about 50% of all CP patients will undergo surgical treatment at some time point in the course of the disease. [29] Surgical intervention is mandated if pain no longer responds to analgesics or if complications in the adjacent organs occur, such as common bile duct obstruction, pancreatic duct obstruction, duodenal obstruction, or major vascular involvement. [30-31] Additionally, the exclusion of pancreatic cancer is sometimes not possible even with all the available diagnostic procedures, and only surgical resection can provide a definite answer. Recently, some studies have shown that surgery can also have a positive influence on the further course of the disease, postponing the final "burn-out" of the pancreas and the consequent appearance of exocrine and endocrine insufficiency. [32] Therefore, it is of great clinical importance in the treatment of chronic pancreatitis to address the above-mentioned problems surgically before the disease has progressed to an advanced stage in which exocrine and endocrine function is completely lost.

Surgery in chronic pancreatitis : Indications

Surgical treatment of chronic pancreatitis depends on the localization and the pathomorphological appearance of complicating lesions. However, there is still controversy over which procedure to choose as the surgical standard in this field.

Surgical treatment of chronic pancreatitis can basically be divided into drainage procedures and section procedures. With regard to the preservation of exocrine and endocrine pancreatic function, drainage operations should be considered first. However, there are only a few indications for drainage procedures in chronic pancreatitis which can lead to good long-term results. If drainage procedures are used without strong indications, the long-term results are poor.

The second option to treat CP is resection. The classical Whipple resection was the standard operation in chronic pancreatitis for several decades. [33] However, in the last two decades, the classical Whipple resection has been steadily replaced by organ-preserving surgical procedures, such as the pylorus-preserving Whipple resection and the duodenum-preserving pancreatic head resection. [4,30,34-37] In the following pages we will give an overview of the surgical techniques most frequently used in the treatment of chronic pancreatitis. Nevertheless, in our opinion the duodenum-preserving pancreatic head resection is the treatment of choice to treat patients with pancreatic head-related complications. Drainage procedures

If we consider that the major goal of surgery in chronic pancreatitis is the relief of intractable pain while preserving as much endocrine and exocrine function as possible, and if the theory of pain generation is based on increased intrapancreatic ductal and parenchymal pressure, then it is logical to try and achieve pain relief with drainage of a dilated pancreatic duct.

Looking back at the history of pancreatic surgery, three drainage procedures have been often used : sphincterotomy, caudal pancreaticojejunostomy and longitudinal pancreaticojejunostomy (Partington-Rochelle). Only the last of these still has some good indications for performance today. The Partington-Rochelle procedure is especially indicated if imaging during the diagnostic workup demonstrates a dilated pancreatic duct and the endoscopic retrograde cholangiopancreaticography (ERCP) shows the obstruction. The degree of main pancreatic ductal dilatation necessary to obtain satisfying results with this procedure is still controversial : the recommendations range from 3 mm to 8 mm. According to the technique as described by Partington and Rochelle, [38] construction of the longitudinal pancreaticojejunostomy anastomosis with a Roux-en-Y jejunal loop is followed by a complete drainage of the Wirsung and the Santorini ducts along the whole pancreas. The Partington-Rochelle operation is a safe technique - current results show an operative mortality of between 0% and 5% and an operative morbidity rate of 20% to 25%. Concerning the main goal of relieving persistent pain, the literature shows results of around 65% (and even of 80% over the short term). [39-42]

A main shortcoming of the longitudinal pancreaticojejunostomy is the frequently observed concomitant presence of pancreatic head enlargement by an inflammatory mass. This complicates the adequate drainage of the pancreatic head and therefore can frequently lead to the failure of the method. The only way to address this problem is to perform a resection of the pancreatic head.

PANCREATIC RESECTION

The classical Whipple resection

In search of a therapy for malignant processes in the pancreatic head, Walter Kausch performed the first successful radical pancreaticoduodenectomy in 1909, [43] followed by Whipple in 1935. [33] Both men used a two-stage procedure which preserved the antrum and pylorus of the stomach. In 1945 Whipple published a technical modification that included the resection of the antrum and the pylorus as well. [44] The success of this new technique was first clouded by its significant perioperative morbidity and mortality. Later in this century the Whipple resection was also adopted for the treatment of benign pancreatic disorders like chronic pancreatitis. Over the years the Whipple procedure has become progressively safer and present reports show a hospital mortality under 5%. [45-47] As safety improved, the Whipple resection was used more and more frequently also in patients with chronic pancreatitis, and until recently it served as the standard operation in this disease.

However, quality control studies following the classical Whipple resection have shown that the operation’s long-term results are unsatisfactory. The data are especially disappointing with regard to quality of life : there is often poor postoperative digestive function, including dumping, diarrhoea, peptic ulceration and dyspeptic complaints. In addition, the classical Whipple resection often leads to diabetes mellitus, which is responsible for the high late-postoperative morbidity and mortality in patients with chronic pancreatitis. [48-50]

There is no reason to treat a benign pancreatic disease with a radical oncological operation which removes a part of the stomach, the duodenum, the gallbladder and extra-hepatic bile duct, which are only secondarily involved in the pancreatic disease. This fact has led to the development of newerorgan-preserving procedures to treat the complications caused by chronic pancreatitis.

The pylorus-preserving Whipples resection

The pylorus-preserving Whipple resection (pylorus-preserving pancreatico-duodenectomy) was originally introduced to treat malignant pancreatic head tumours, and represented a more "organ-preserving" alternative to the classical Whipple . [51]

Apparently, Kausch was the first to perform this operation. The original report from Kausch in 1909 describes a two-stage procedure for resection of a periampullary tumour by dividing the duodenum distally from the pylorus. [43] But Kausch finally performed the reconstruction through a gastroenterostomy, so that he didn’t take advantage of preserving the stomach and the pylorus. This surgical technique was reestablished by K. Watson in 1942 [51] and re-introduced by W. Traverso and W. Longmire in 1978, [35] and was popularized as an alternative to the classical Whipple resection. Watson argued that the preservation of the entire stomach and the pylorus should lead to better postoperative results regarding gastrointestinal hormonal secretion, and so should be beneficial for digestion. He demonstrated that there was a reduction in postoperative ulcerations, which are frequent side effects of partial gastrectomy. By preserving the stomach, the pylorus and the first part of the duodenum, the pylorus-preserving Whipple resection protects against the postgastrectomy syndrome, including gastric dumping. It allows normal digestion of food by maintaining the volume and mixing function of the stomach. Even more, the preservation of the pylorus prevents the reflux of bile and pancreatic juice, which might lead to an alkaline gastritis and eventually to the development of gastric ulcerations.

Recent studies report a hospital mortality of between 0% and 4% after pylorus-preserving Whipple resection. [35,36,52-57] By far the most common postoperative complication, reported in about 30% of the patients, is subsequent problems with gastric emptying. [51,52] However, several studies have demonstrated that gastric emptying is only a transient problem and that the majority of patients have no long-term alteration in gastric emptying pattern. However there is a definite risk of developing postoperative cholangitis and marginal ulcerations after pylorus-preserving Whipple resection.

Concerning long-term complications of the procedure, there is substantial deterioration in the exocrine and endocrine pancreatic function. More than one third of the patients who have had a pylorus-preserving duodeno-pancreatectomy will need oral enzyme supplementation, and nearly 50% of the patients develop an insulin-dependent diabetes mellitus in the first 5 years after the operation. [58-61]

Regarding quality of life, the pylorus-preserving Whipple resection provides satisfying results. There is weight gain in around 90% of the patients postoperatively. [53,59] Furthermore, the operation leads to long-lasting pain relief in 85% to 95% of the patients during the first 5 years postoperatively. [53,54,59]

Pancreatic left resection

About twenty years ago pancreatic left resection was a standard operation for treating chronic pancreatitis.62 There are two forms of pancreatic left resection : partial left resection, which includes the removal of about half of the organ, and subtotal pancreatectomy, which includes the removal of approximately 95% of the pancreas.

However, as mentioned before, in many patients the head of the pancreas is the principal focus of chronic pancreatitis. Pancreatic head enlargement, which is based on an inflammatory process, is present in most patients, and is thought to be the source of the severe pain associated with chronic pancreatitis. [63] Thus the use of pancreatic left resection in these patients will lead to poor postoperative pain relief. [64] In addition, resection of the pancreatic body and tail, where most pancreatic islets are located, often leads to insulin-dependent diabetes mellitus, which is responsible for the high late mortality and morbidity seen in patients with chronic pancreatitis. Therefore, the adequacy of pancreatic left resection is questioned in many patients with chronic pancreatitis.64 It is logical that over the past years pancreatic left resection has been replaced by operations which take care of the pancreatic head-related complications and do not affect the pancreatic tail, which often is not the cause of recurrent abdominal pain and pancreatitis-related problems.

Furthermore, improved understanding of the pathophysiology, pain theory and surgical therapy in patients with chronic pancreatitis have placed pancreatic left resection in clear disfavour over the last ten to twenty years. Nevertheless, there are still few indications for partial left resection, such as chronic pancreatitis limited to the body and tail region, persistent or bleeding pseudocysts, and chronic pancreatitis with splenic hypertension, based on a splenic vein thrombosis. With a good preoperative diagnostic work-up, including computed tomography (CT) scanning and endoscopic retrograde cholangiopancreaticography (ERCP), the evaluation of distribution of the disease in the pancreas is possible. In this way a careful selection of the patients who can profit from pancreatic left resection can be worked out preoperaively. Favourable long-term results can only be achieved when pancreatic left resection is performed for the right indication. For this small but specific subgroup of patients, the operation continues to have a place in the surgical treatment of chronic pancreatitis.

Duodenum-preserving pancreatic head resection : An organ preserving operation

The duodenum-preserving pancreatic head resection was introduced in 1972 by Hans Beger to treat pancreatic head-related complications of patients with chronic pancreatitis. [63,65,66] In this procedure the pancreatic head is resected subtotally by preserving the body and tail of the pancreas, the duodenum, the pylorus, and the extrahepatic bile tract. With this operation, the normal anatomy of the upper gut and the normal food passage through the stomach and the duodenum are preserved (Fig. 1). The guiding principle in this modern operation is to treat and remove only the specific structures which are involved in the inflammatory process in the pancreatic head. Consequently, the left part of the pancreas is mostly preserved and there is generally no major restriction of exocrine and endocrine function of the pancreas.

 
Fig 1: Reconstruction following duodenum preserving pancreatic head resection.

Candidates for duodenum-preserving pancreatic head resection are generally patients with severe chronic pancreatitis who are suffering from pancreatitis-related complications which cannot be treated effectively with conservative therapy.

In 298 patients who underwent a duodenum-preserving pancreatic head resection, common bile duct stenosis was found preoperatively in 48% (144/298), compression of the peripancreatic vessels-especially of the portal vein - in 17% (52/298), and some degree of duodenal stenosis in 32% (95/298). Pronounced macromorphological alterations in the pancreatic head were usually seen, with development of small pseudocysts, necrosis, and pancreatic stones.

The operative procedure used in the duodenum-preserving pancreatic head resection is described in several articles, and has been shown to have an excellent postoperative outcome and low mortality and morbidity rates. [37,4,63,65,66] Our large series conducted with 298 patients shows the following results. [67]

Of the total 298 patients, 17 (5.7%) had to undergo reoperation due to early postoperative complications. These included intestinal bleeding (n=3), leakage of the anastomosis (n=5), an intraabdominal abscess (n=3), postoperative ileus (n=2), a common bile duct stenosis (n=1), a duodenum wall ischaemia (n=1), ulcer perforation (n=1) and sepsis (n=1). The median postoperative hospitalization time was 13 days (range 7-59 days). One patient died due to a fulminate embolism of the pulmonary artery and two others died due to sepsis after leakage of the anastomosis, corresponding to a hospital mortality rate of 1.01% (3/298).

In 1994 a long-term follow-up (median follow-up 6 years) was carried out. Forty patients (13%) were lost for follow-up and 258 patients were available for final evaluation. 23 patients died in the later postoperative course and 3 died perioperatively. 187 of the 232 (81%) experienced an increase in weight postoperatively. 143 of 232 (62%) were pain-free and 61 of 232 (26%) reported rare episodes of pain. The professional rehabilitation rate was 63% (147/232). Eleven patients (5%) were unemployed and 74 patients (32%) were retired. Endocrine pancreatic function before and after duodenum-preserving pancreatic head resection compared favourable.

These data demonstrate the clear advantage of the duodenum-preserving pancreatic head resection over the Whipple procedures (classical and pylorus-preserving) with regard to the normal postprandial regulation of the digestive process. By preserving the extrapancreatic organs such as the stomach and the duodenum, this procedure leads to a normal food passage and so to a normal glucose metabolism after surgical intervention.

The Frey procedure : A modification of the duodenum-preserving pancreatic head resection

In 1985 Frey and Smith [68] introduced a modification of the duodenum-preserving pancreatic head resection. They did a local resection of the pancreatic head without dividing the pancreas, in combination with longitudinal pancreaticojejunostomy. [38,68-70] In this way they combined two principles of surgery in chronic pancreatitis : partial pancreatic head resection and drainage procedures.

In a trial enrolling 50 patients (mean follow-up period of 37 months), Frey et al. [70] reported no operation-related mortality and found that postoperatively 75% of the patients were pain free. Comparable results were demonstrated by Izbicki et al in a prospective randomized study (mean follow-up period of 1.5 year) comparing the Frey operation and the duodenum-preserving pancreatic head resection. [71] The only difference they found between the two procedures was lower postoperative morbidity after the Frey procedure (11%, vs. 21% after the duodenum-preserving pancreatic head resection).

Both the Frey procedure and the duodenum-preserving pancreatic head resection seem to be safe and effective in the management of pain and for dealing with complications arising from neighbouring organs of the pancreas. However, experience with and long-term follow-up for the Frey procedure are too limited to make a definitive judgment at this point regarding its clinical value as a surgical treatment option in chronic pancreatitis.

What should be the gold standard in surgery of chronic pancreatitis today?

In the last years several prospective randomized studies had been performed to compare various surgical techniques for treatment of chronic pancreatitis :

- Comparison of the classical Whipple resection and the duodenum-preserving pancreatic head resection. [72]

- Comparison of the pylorus-preserving Whipple and the duodenum-preserving pancreatic head resection. [30]

- Comparison of the Frey procedure and the duodenum-preserving pancreatic head resection. [71]

In the first two trials it was clearly demonstrated that the duodenum-preserving pancreatic head resection is superior to the classical Whipple resection as well as to the pylorus-preserving Whipple with regard to higher efficacy of long-term pain relief and preservation of postoperative exocrine and endocrine pancreatic function. [30,72]

As already mentioned, the comparison of the Frey procedure and the duodenum-preserving pancreatic head resection showed no significant difference other than beside lower postoperative morbidity rate with the Frey procedure. [71] This fact is not surprising if we take into account that there are not big technical differences between the two procedures with the exception of the dissection above the portal vein. Therefore, duodenum-preserving resections of the pancreatic head should today replace the Whipple operations (classical and pylorus preserving) and they should be considered as the standard surgical treatment in patients with chronic pancreatitis and pancreatic head related complications.

CONCLUSION

In conclusion, although CP continues to be a baffling disease, significant advances in the understanding of the various pathophysiological mechanisms have been achieved over recent years. As a result of these developments, treatment strategies based on findings of molecular biology are likely to play a major role in the coming years.

On the surgical front, the accent is more towards organ-preserving surgery. Thus the duodenum preserving pancreatic head resection and their modifications seem to be the preferred choices over the more morbid Whipple procedures which should be restricted to malignant pathologies.

ACKNOWLEDGEMENT

Dr. Shailesh V Shrikhande acknowleges the receipt of the special training grant from R.D.B.S.K. of BHT, Mumbai.

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