The Evolution of the Surgical Treatment of Chronic Pancreatitis

REVIEW

Dana K. Andersen, MD,* and Charles F. Frey, MD†

of the pancreatic parenchyma, which leads to stricture formation and Objective: To establish the current status of surgical therapy for chronic obstruction of the main and accessory ducts with or without intra- pancreatitis, recent published reports are examined in the context of the ductal calcifications. If the obstruction is not relieved these anatomic historical advances in the field. changes may become irreversible. Although the correlation of duct Background: The basis for decompression (drainage), denervation, and diameter, ductal hypertension, and severity of pain have been resection strategies for the treatment of pain caused by chronic pancreatitis inconsistently demonstrated,5–7 preoperative pain severity has been is reviewed. These divergent approaches have finally coalesced as the head correlated with pancreatic histopathology obtained at operation; of the pancreas has become apparent as the nidus of chronic inflammation. small cysts, foci of acinar cell necrosis, and areas of acute inflam- Methods: The recent developments in surgical methods to treat the compli- mation are associated with the most severe intractable pain preop- cations of chronic pancreatitis and the results of recent prospective random- eratively.8 ized trials of operative approaches were reviewed to establish the current best Inflammatory damage to the sensory nerves of the pancreas is practices. also seen in chronic pancreatitis,9,10 and the neuron-specific protein- Results: Local resection of the pancreatic head, with or without duct ase-activated receptor 2 has been found to mediate the pain response drainage, and duodenum-preserving pancreatic head resection offer out- of pancreatic inflammation.11 A subpopulation of sensory neurons comes as effective as pancreaticoduodenectomy, with lowered morbidity and known as C fibers contain peptides such as substance P, neurokinin mortality. Local resection or excavation of the pancreatic head offers the A, and calcitonin-gene related peptide which can cause inflamma- advantage of lowest cost and morbidity and early prevention of postoperative tory changes,12 and recent evidence suggests that neural inflamma- diabetes. The late incidences of recurrent pain, diabetes, and exocrine tion due to proteinase-activated receptor 2 activation or other me- insufficiency are equivalent for all 3 surgical approaches. diators may be a primary cause, and not merely an effect, of Conclusions: Local resection of the pancreatic head appears to offer best pancreatitis. Although these pain mechanisms may be operative in outcomes and lowest risk for the management of the pain of chronic patients with chronic pancreatitis, damage to the sensory nerves may pancreatitis. have special significance in so-called “small duct disease.” In many (Ann Surg 2010;251: 18–32) patients the sensory nerves appear increased in number and abnor- mal in appearance suggesting that nerve damage from inflammation may be the principal source of pain in patients without evidence of ductal hypertension.10 Regardless of the mechanism of pain development, the med- perative approaches to the treatment of chronic pancreatitis ical treatment of chronic pancreatitis-associated pain usually fails, in Ohave undergone a dramatic a transformation over the past few that narcotic dependency occurs in almost all patients. Lankisch et al decades as the head of the pancreas has become universally appre- showed that long-term medical treatment of chronic pancreatitis is ciated as the nidus of chronic inflammation. Furthermore, prospec- associated with diminished analgesic requirements after 2 decades tive, randomized trials have repeatedly shown the superiority of of treatment, but at a cost of almost universal endocrine dysfunction surgical treatment over medical approaches to management. Since and permanent disability.13 In contrast, surgical treatment of chronic the publication of the definitive “History of the Pancreas” by pancreatitis has been shown to eliminate pain and return patients to Howard and Hess in 20021 as well as other recent reviews,2,3 new predisease employment and quality-of-life status.14–18 information and the results of prospective trials have further clarified Operative procedures designed with the objective of elimi- the value of the latest “hybrid” approaches to the treatment of this nating pain and treating the complications of chronic pancreatitis disease. Therefore, we provide this updated perspective on the have historically been classified into 1 of 3 categories: decompres- surgery for chronic pancreatitis. sion of diseased and obstructed pancreatic ducts, denervation of the pancreas, or resection of the proximal, distal, or total pancreas. INDICATIONS FOR SURGERY Surgical denervation strategies have proven to be ineffective or The principal symptom which prompts the diagnosis and infeasible as first-line treatment, so that until recently, the choice of treatment of chronic pancreatitis is pain. Currently, the 2 most operation focused on the dichotomy of decompression versus resec- plausible theories of pain causation in chronic pancreatitis are ductal tion. Within the past few years, however, a category of hybrid hypertension with activation of stretch fibers and peripancreatic procedures has been shown to be safe and effective. These newer sensory nerve damage.4 techniques combine limited resection with decompression, and Ductal hypertension with an accompanying tissue compart- achieve the effectiveness of long-term pain relief usually associated ment syndrome is thought to result from inflammation and fibrosis with resectional procedures as well as low rates of morbidity and mortality typical of decompression approaches.

From the *Departments of Surgery, Johns Hopkins Bayview Medical Center, Balti- DECOMPRESSION PROCEDURES more, MD; and †Department of Surgery, University of California, Davis Campus, Sacramento, CA. In 1898, Gould reported having successfully removed calculi Reprints: Dana K. Andersen, MD, Department of Surgery, Johns Hopkins Bay- from Wirsung’s duct19 and in 1902 Moynihan removed a calculus view Medical Center, 4940 Eastern Ave, Baltimore, MD 21224. E-mail: from the pancreatic duct and astutely declared that timely removal of [email protected]. ductal calculi, by either the transpancreatic route, later described by Copyright © 2009 by Lippincott Williams & Wilkins 20 ISSN: 0003-4932/10/25101-0018 Mayo-Robson in 1908, or transduodenally through the papilla of DOI: 10.1097/SLA.0b013e3181ae3471 Vater, would prevent “atrophy of the pancreas” and relieve pain,

18 | www.annalsofsurgery.com Annals of Surgery • Volume 251, Number 1, January 2010 Annals of Surgery • Volume 251, Number 1, January 2010 Surgery of Chronic Pancreatitis

nausea, and vomiting.21 By 1939, Haggard and Kirtley were able to find 65 operative reports in which calculi were removed from the pancreatic duct.22 The mortality rate was 18%, however, and long term follow-up was absent. The association of biliary calculi with acute and chronic pancreatitis was noted by Opie, Halsted, and others in the early 20th century.23–25 By the 1950s, biliary stone disease was widely observed to be a common factor associated with acute and recurrent pancreatitis in the elderly and in regions such as the United King- dom. In North America, Doubilet and Mulholland advocated decompressing the proximal pancreatic and distal bile ducts by sphinc- teroplasty to prevent recurrent pancreatitis,26,27 but this strategy failed in cases where biliary disease was not the culprit. External drainage of the pancreatic duct to decompress obstruction caused by stricture or calculus was first described by an Indiana gynecologist Goethe Link in 191128,29 (Fig. 1). The lasting success of his single case established the validity of decompression in the treatment of obstructive pancreatopathy. The frequent association of parenchymal and ductal calcifications with chronic pancreatitis subsequently became widely appreciated, in large part, due to the meticulous study of the disease by Comfort et al at the Mayo Clinic.30 Chronic calcific pancreatitis became a separate entity when it was appreciated that the pancreatic FIGURE 2. DuVal’s caudal pancreaticojejunostomy. In 1954, duct calculi caused an obstructive pancreatopathy that could be M. K. DuVal described the technique of drainage of the tail of treated by decompression. the pancreas into a Roux-en-Y loop of jejunum (Reprinted with Internal drainage of an obstructed pancreas followed the techni- permission from Greenlee HB, Chronic pancreatitis. In: Moody cal development of methods to safely anastomose the retroperitoneal FG, Carey LC, Jones RS, et al, eds. Surgical Treatment of Diges- organ with the intestine. The Swiss surgeon, Cesar Roux, described his tive Diseases. Chicago, IL: Yearbook Medical Publishers; 1986: defunctionalized loop of jejunum as a method of draining the remnant 494). of stomach after gastrectomy in 1897,31 and Desjardins in 190732 and Coffey in 190933 both proposed using an intestinal conduit for drainage of the pancreas after conducting studies on dogs. In 1947, Cattell described a Roux-en-Y, side-to-end, pancreaticojejunostomy as effective palliation for obstructive pancreatopathy secondary to malignancy.34 In 1954, Duval35 and separately Zollinger et al36a both described the caudal, end-to-end, pancreaticojejunostomy as a drainage procedure for chronic pancreatitis (Fig. 2). These efforts at duct decompression inevitably failed, however, as a result of recurrent or progressive segmental stenosis of the pancreatic duct, which was subsequently described by Puestow and Gillesby as a “chain-of-lakes” appearance of the duct.36 They reported good results with a longitudinal decompression of the body and tail of the pancreas into a Roux limb of jejunum (Fig. 3). Four

FIGURE 3. Puestow and Gillesby’s longitudinal pancreaticojejunostomy. In 1958, C. B. Puestow and W. J. Gillesby described an invaginating caudal pancreaticojejunostomy which was created after opening the pancreatic duct throughout the body and tail of the gland (Reprinted with permission from Greenlee HB. Chronic pancreatitis. In: Moody FG, Carey LC, Jones RS, et FIGURE 1. Link’s pancreatostomy. In 1911, Goethe Link dis- al, eds. Surgical Treatment of Digestive Diseases. Chicago, IL: covered an obstructed pancreas with intraductal calculi in a Yearbook Medical Publishers; 1986:494). young woman with chronic pain. He fashioned a tube decompression after mobilizing the distal gland, and the woman lived for many years requiring only occasional tube of 21 initial cases of Puestow and Gillesby were constructed as maintenance (Reprinted with permission from Ann Surg. side-to-side anastomosis, and 2 years after their report, in 1960, 1911;53:768–782). Partington and Rochell described in detail the side-to-side longitu-

scopic treatment in randomized clinical trials in which the long, side-to-side technique of pancreaticojejunostomy is employed.47,48 Although the Puestow procedure became the standard drainage procedure for close to 40 years,49,50 it was evident that not all patients with chronic pancreatitis had dilated ductal disease.51 More- over, despite early postoperative pain relief observed in 80% of patients, recurrent pain developed within 3 to 5 years in up to 30% of patients after the Puestow procedure.49–51 The recurrence of pain was often attributed to persistent or recurrent disease in the head of the pancreas.52 In addition to its failure to address ductal disease in the head of the pancreas, technical problems with the Partington and Rochelle operation can contribute to recurrent symptoms. In ducts less than 5 mm in diameter, the anastomosis can be difﬁcult. Izbicki et al proposed a solution to the problem of small ducts or segments of discontinuous ducts, by creating a channel or groove in the parenchyma overlying the duct, thereby allowing a patent and permanent decompression.53 Nevertheless, the principal cause of failure of the Puestow operation is the lack of adequate decompression of the proximal duct of Wirsung, as well as the uncinate and tributary ducts in the head of the pancreas.54

DENERVATION PROCEDURES In 1947, Bronson Ray, chief of Neurologic Surgery at the New York Hospital-Cornell Medical Center, and his colleague C. L. Neill studied the effects of pancreatic stimulation during laparotomy FIGURE 4. Partington and Rochelle’s modification of under local anesthesia before and after thoracolumbar sympathec- Puestow and Gillesby’s procedure. In 1960, P. F. Partington tomy. Bilateral, but not unilateral, sympathectomy led to complete and R. E. Rochelle described the side-to-side Roux-en-Y pan- relief of pain from traction or electrical stimulation of the pancre- creatico-jejunostomy which became known as the Puestow as.55 In 1950 Ray and Console reported the results of bilateral procedure (Reprinted with permission from Greenlee HB. sympathectomy in 4 patients with pain from chronic pancreatitis, Chronic pancreatitis. In: Moody FG, Carey LC, Jones RS, et with mixed results.56 A spate of reports followed, most of which al, eds. Surgical Treatment of Digestive Diseases. Chicago, IL: included only a handful of patients and with a follow-up which Yearbook Medical Publishers; 1986:494). infrequently exceeded a year.57–59 Of 11 patients followed more than 1 year, Phillips reported that only 2 were improved.60 Over the intervening years many surgeons have attempted to dinal pancreaticojejunostomy that became known as the “Puestow” improve on these results, but without great long-term success. procedure37 (Fig. 4). Results of recent studies show significant reductions in pain assess- Although the side-to-end or caudal end-to-end pancreaticoje- ment and narcotic use in the first year after bilateral thoracic junostomy proved insufficient for decompression of the entire ductal splanchnicectomy.61 However, studies with follow-up extending 2 system in chronic pancreatitis, the use of an intestinal conduit has years or more disclose that narcotic usage increases and pain long been employed successfully for internal drainage of pancreatic typically returns to preoperative levels.62,63 In 15 patients followed pseudocysts and fistulas. The concept of Roux-en-Y drainage of a by Maher et al for up to 6 years, only 3 remained narcotic free at the pseudocyst was first described by Duncombe in 1929,38 and this end of this period.64 Howard et al reported that of 38 patients who remains the preferred method of internal drainage when cystogas- had operative or endoscopic interventions before bilateral thoracic trostomy or cystoduodenostomy is infeasible. Pancreatoenterostomy splanchnicectomy, most returned to pretreatment status at 12 months had been employed by Kausch for the treatment of pancreatic fistula as measured by pain scores, narcotic usage, symptom scales, and as early as 191239 although the standards for diagnosis and surgical quality of life measures.65 Of interest, he found that patients who treatment of pancreatic fistulas did not become routine until after the had had no prior operative or endoscopic intervention before bilat- widespread use of endoscopic retrograde cholangiopancreatography eral splanchnicectomy and who likely had “small duct” disease in the 1970s.40 remained improved throughout the period of follow-up. Further For long-term relief of pain in chronic pancreatitis, techniques study of this subgroup of patients is needed to support or refute this of focal decompression of the ductal system were found to fail as observation. multiple points of obstruction due to calculi or strictures are the rule Celiac neurolysis has been used for decades to treat the pain in patients with alcoholic, hereditary, tropical, and idiopathic pan- of advanced pancreatic malignancy, and has been shown to be creatitis. With the advent of therapeutic endoscopy and techniques effective and long-lasting when performed with local injection of for transluminal stone removal and lithotripsy, modern clinical 50% alcohol.66 The use of operative, endoscopic, and image-guided series have reported the successful endoscopic treatment of pancre- neurolysis of the celiac trunks and ganglia have been reported in the atic duct calculi, although the long-term outcomes of these efforts treatment of chronic pancreatitis, with variable results.67 Because has been uneven.41–44 Endoscopic removal of pancreatic duct stones long-term survival of the patient is the goal, the use of alcohol as a is usually coupled to prolonged pancreatic duct stenting, which neurolytic agent has generally been avoided in patients with chronic carries the risk of further inflammation.45,46 Despite the risk of pancreatitis, but substitution with long-acting “-caine” derivatives perioperative complications, the surgical management of pancreatic such as bupivacaine have yielded disappointing results. Immediate duct stones and stenosis has been shown to be superior to endo- and short-lived pain relief is commonly reported, although long-term

ischemia, removal of the diseased pancreatic tissue and duct system would seem curative. Perversely, however, the more pancreatic tissue that is excised, the greater the risk of inducing pancreatic endocrine and exocrine insufficiency, with a very morbid outcome. Although exocrine function can be replicated with exogenous enzyme administration, the endocrine dysfunction of subtotal and total pancreatectomy has proven difficult to overcome and is often fatal.73–75 Until the mid-1970s, when computerized tomography and endoscopic retrograde cholangiopancreatography became widely available, the inability to document the ductal anatomy of the diseased pancreas contributed to a preference for resection as the only definitive method of treating the chronically diseased gland. Patients who might have been candidates for a decompression procedure often went unidentified, and the failure of early attempts FIGURE 5. Denervated splenopancreatic flap. In 1984, W. D. at decompression in small-duct glands led to a bias that only the Warren et al described a procedure in which the central por- most dilated ductal systems were truly helped by decompression tion of the pancreatic head was resected with sparing of the procedures. duodenum after transection of the neck of the gland, and Proximal Pancreatectomy the body and tail were perfused retrogradely through the splenic hilum (Reprinted with permission from Surg Gynecol Pancreaticoduodenectomy has been performed for over 60 Obstet. 1984;159:581–583). years, longer than any other operation used in the management of chronic pancreatitis. It has proven to be an effective means of managing pain and the complications of chronic pancreatitis.14,76–80 In spite of extensive experience with the operation by many distin- 68 pain relief is rare. As a result, multiple procedures are required and guished surgeons over a prolonged period, pancreaticoduodenec- symptoms usually recur. tomy remains a work in progress due to many unresolved technical, Vagotomy, with partial gastrectomy or a drainage procedure, physiological, and nutritional issues. has been examined in patients with chronic pancreatitis and found to After Whipple’s description in 1946,81 the application of the offer little benefit. Cahow and Hayes examined the extent of pain proximal pancreaticoduodenectomy to the treatment of chronic pan- relief after vagotomy and pyloroplasty plus celiac plexus injection creatitis was slow, however, and until the 1970s, relatively few 69 with absolute alcohol in 6 patients. All did well for up to 24 pancreaticoduodenectomies were performed, largely due to a per- months, but it is likely that the long-term pain relief was largely due sistently high perioperative mortality rate of about 30%.82 Since that to the celiac neurolysis. Although vagal efferent and afferent path- time, however, the use of pancreaticoduodenectomy has grown ways are now appreciated as fundamental to pancreatic exocrine dramatically, due to advances in perioperative management and due 70 regulation, truncal vagotomy is not recommended as a means to to the dedication of a number of distinguished pancreatic sur- relieve the pain of chronic pancreatitis. geons.83–85 In 1984, Warren et al described the “denervated splenopancreatic flap” for chronic pancreatitis.71 The operation consisted of Outcomes, Mortality, and Morbidity dividing the neck of the pancreas over the portal vein as would be In the 3 largest modern (circa 2000) series of the treatment of done in a pancreaticoduodenectomy or duodenum-preserving pan- chronic pancreatitis by the Whipple procedure, pain relief 4 to 6 creatic head resection (DPPHR) (Fig. 5). The majority of the head of years after operation ranged from 71% to 89% of patients.14,76,77 the pancreas was resected, as in the 95% pancreatectomy or the Although the mortality rate of the operation has been reduced to less DPPHR, leaving a small cuff of pancreatic tissue along the inner aspect than 5% in high volume centers, the morbidity stubbornly remains at of the duodenum. The splenic artery was divided at its origin and the about 40%.14,76,77 splenic vein at its junction with the superior mesenteric vein. The body and tail of the pancreas was then freed from the retroperitoneal Pylorus Preservation tissue “until the pancreas is attached only to the vessels at the splenic The introduction of the pylorus-preserving pancreaticoduode- hilus. This severs somatic nerve fibers as well as autonomic afferent nectomy (PPPD) in chronic pancreatitis by Traverso and Longmire fibers along the splenic artery.” The transected neck of the pancreas in 197886 was enthusiastically adopted by the pancreatology com- was then anastomosed to a Roux-en-Y limb. munity because of presumed nutritional and physiologic benefits In a series of 5 such operations reported by Shires et al, pain associated with retention of the pylorus.15,87 The technique was first 72 control was reportedly good in 3 patients and fair in 2 patients. described by Watson in 194488 as a modification of the distal Weight gain occurred in all 5 patients and 4 of 5 were considered gastrectomy-requiring procedure described by Whipple 10 years rehabilitated. Long-term results were never reported on this techni- earlier. After having been ignored until Traverso and Longmire’s cally challenging procedure, and no other surgical group has re- report, the pylorus-preserving technique is now employed in 70% to ported any experience with this operation. It is likely that the 80% of all Whipple procedures.76,77,80 Although physiologic gastric long-term effects on pain relief were ascribable to the (duodenum- emptying is assumed with preservation of the pylorus, the presumed preserving) pancreatic head resection which accompanied the pro- nutritional benefits have never been well substantiated, and in fact cedure. some studies have shown no significant nutritional differences between the PPPD and the “standard” Whipple procedure.89,90 Still RESECTIONAL PROCEDURES others have suggested an increased incidence of marginal ulceration Partial or total resection of the pancreas is a seemingly after the pylorus-preserving technique.76 Most studies have docu- attractive and definitive solution to the vexing problem of pancreatic mented an improved quality of life after the pylorus-preserving pain. Whether the pain results from inflammation affecting the version of the Whipple procedure,15,87,91,92 but others support the nerves, ductal hypertension, compartment syndrome, or chronic use of the standard technique.76,77,89

Anastomotic Leak patients with pancreatic cancer 1 year after pancreaticoduodenec- 110 Pancreatic anastomotic leak is a major cause of prolonged tomy. hospital stay and intra-abdominal infection. The incidence varies The use of either internalized or externalized pancreatic duct from 6% to 28% in series which include both malignancy and stents to ensure patency of the anastomosis has been advocated, and chronic pancreatitis, and is dependent on the definition of a currently stents are used in half of all the Whipple procedures leak.85,89,93–96 Although pancreatic anastomotic leaks are less likely performed by high-volume surgeons.95 Although a randomized to occur in chronic pancreatitis because of the firmer consistency of prospective trial has demonstrated a reduced leak rate with stent use the gland, the dorsal duct can be 2 to 3 mm or less in a gland with in a mixed group of patients,111 it is unclear whether stent use alters diffuse sclerosis, and difficulties with the anastomosis can occur. A the rate of leak in patients with chronic pancreatitis. Complications variety of techniques of anastomoses have been employed, including such as stent migration have been reported, and alterations of the the end-to-side duct to mucosa technique, as well as the invaginating pancreatic duct can occur when stents are left for months or or intussuscepting methods of end-to-end anastomosis. longer.112,113 Most of the data on the success or failure of various techniques of anastomosis comes from patients with pancreatic cancer Major Perioperative Complications and may not be applicable to patients with chronic pancreatitis. The Life threatening postoperative complications which occur duct-to-mucosa anastomosis leak rate has been reported to be as low rarely after pancreaticoduodenectomy include the development of as 1%,97 considerably less than the 10% to 12% leak rate observed necrotizing pancreatitis in the remaining pancreas, which may re- with the intussuscepting or invaginating technique (Fig. 6).95,98,99 quire completion pancreatectomy, and intraluminal bleeding from a Recently, modifications in technique have been shown to reduce the pancreatic artery or from erosion by the gastroduodenal artery into leak rate of the duct-to-mucosa technique further, including the use the jejunal limb. Such complications are more commonly associated of the operating microscope to visualize clearly the duct-to-mucosa with cancer of the pancreas, but fatal complications do occur in anastomosis,100 and the stripping away of the serosa of the jejunal patients with benign disease.14,76,77,114,115 limb where the cut end of the pancreas will reside after completion of the duct-to-mucosa portion of the anastomosis.101 Finally, a Late Complications randomized, prospective trial of a new invaginating technique in Long-term complications of the pancreaticoduodenectomy which the jejunum is secured around the pancreas with a purse- 102 include stricturing of the anastomoses leading to pain recurrence and string suture has claimed no leaks in over 100 cases. Further the loss of exocrine and endocrine function in the remaining pan- refinements and consensus on these technical details await multisite, creas116,117; the late incidence of both exocrine and endocrine prospective randomized trials. Prospective, randomized trials of the dysfunction after pancreaticoduodenectomy is about 50%. Telford use of octreotide administered postoperatively to prevent leak have 103,104 98,105 and Mason reported a reduced incidence of anastomotic stricture both supported and refuted its value, and the use of fibrin 117 106 when the “stuffing” or invaginating method is avoided. The rates glue appears ineffective. of dysfunction are higher when reconstruction of pancreaticoenteric Pancreaticogastrostomy has been advocated as safer and eas- 97,107 drainage is avoided altogether by performing a ligation of the ier to perform than the end-to-side pancreaticojejunostomy. pancreatic duct, as advocated in older series, and some groups Randomized, controlled trials which have compared the 2 tech- continue to advocate this technique.118 niques have come to different conclusions as to whether the leak rate Delayed gastric emptying has been reported as an early or the operating time differs between these methods,108,109 and Jang postoperative complication, which usually resolves spontaneously, et al found no functional differences between the 2 anastomoses in or as a late complication associated with a retrocolic, as opposed to an antecolic, gastrojejunostomy.119–122 The incidence of delayed gastric emptying has been reported to be higher in patients in whom the pylorus was preserved than with the standard operation.123–126 It is unclear whether retention of the pylorus alters the hormonal regulation of gastric function, as suspected by some,127,128 or whether the incidence of delayed gastric emptying is influenced more by other complications than whether the pylorus is preserved.129

Total Pancreatectomy Priestley et al ﬁrst described successful total pancreatectomy in 1944 in a patient with hyperinsulinism,130 and 2 of Whipple’s original 5 cases of chronic pancreatitis reported in 1946 were treated with total pancreatectomy.81 Subsequently, surgeons who employed total pancreatectomy found that the operation produces no better pain relief for their patients than pancreaticoduodenectomy (about 80%–85%). More- over, the metabolic consequences of total pancreatectomy in the FIGURE 6. A, and B, End-to-side, duct-to-mucosa method of absence of islet cell transplantation are profound and life threaten- pancreaticojejunostomy. Note that the length of the enterot- ing. The patients have a “brittle” form of diabetes in which avoid- omy is equivalent to the diameter of the pancreatic duct ance of hyper- and hypoglycemia is problematic.50,74,131,132 In (Reprinted with permission from Bell RH Jr. Atlas of pancre- addition, lethal episodes of hypoglycemia are common in severe atic surgery. In: Bell RH Jr, Rikkers LF, Mulholland MW, eds apancreatic diabetes. These are due to hypoglycemic unresponsive- Digestive Tract Surgery. A Text and Atlas. Philadelphia, PA: ness, due to the absence of pancreatic glucagon, and to hypoglyce- Lippincott Raven; 1996:1059). mia unawareness, despite an on-going need to treat with exogenous

22 | www.annalsofsurgery.com © 2009 Lippincott Williams & Wilkins Annals of Surgery • Volume 251, Number 1, January 2010 Surgery of Chronic Pancreatitis insulin.133 In a series of over 100 patients treated with total pancre- Distal Pancreatectomy (95%) atectomy, Gall et al showed that half of all the late deaths after this In 1956, Child and Donovan reported a 3-year follow-up of a 73 operation were due to (iatrogenic) hypoglycemia. Without ade- 36-year-old woman with a blockage of the major pancreatic duct 2.5 quate insulin treatment, patients with apancreatic diabetes become cm from the ampulla of Vater. The pancreas was resected distal to progressively more hyperglycemic and develop the same incidence the obstruction leaving only 5% to 10% of the pancreas adjacent to 134 of retinal and renal disease as type 1 diabetic patients. Despite the duodenum (Fig. 7). After the operation the patient gained 60 lbs newer forms of insulin and insulin delivery systems, severe pancre- and remained free of pain.148 atic diabetes is an adverse outcome, as complete prevention of the In 1957, Barrett and Bowers reported a successful near total physiological consequences of total pancreatectomy remains an distal pancreatectomy performed 3 years earlier that was almost 135 unfulfilled goal. identical to that performed by Child and Donovan.149 In 1965, Fry and Child reported their experience with 16 patients who had Pancreatectomy With Islet Auto-Transplantation undergone the procedure.9 Child’s rationale for performing the 95% After being largely abandoned in the 1970s, total pancreate- distal pancreatectomy was to avoid a pancreaticoduodenectomy, ctomy for chronic pancreatitis has been increasingly used in recent which he considered an operation associated with high mortality and years in conjunction with islet cell auto-transplantation. Despite the morbidity more suited to the treatment of malignancies. In describ- difficulties in recovering islets from a chronically inflamed gland, ing the importance he attached to preserving the duodenum, Child Najarian et al demonstrated the utility of auto-transplantation of said “(Pancreatico-duodenectomy) removes the distal stomach, the islets in patients with chronic pancreatitis in 1980.136 Subsequently, entire duodenum and normal choledochoduodenal junction. Since through refinements in the methods of harvesting and gland preser- these deprivations seemed unjustified for a non cancerous disease, vation, and through standardization of the methods by which islets we sought another solution to rid patients of a chronically inflamed are infused into the portal venous circuit for intrahepatic engraft- pancreas… In the 95% pancreatectomy… a small cuff of the head of ment, the success of auto-transplantation has steadily increased. the pancreas is preserved. This lines the lesser curvature of the Some degree of insulin dependence is still present in the majority duodenum and is estimated to be no more than 5% of the entire of recipients, but insulin independence is attained in about gland. In addition to retaining some small portion of functioning one-third of patients treated in recent series.137,138 Although 2 to pancreas, the cuff helps to protect the superior and inferior pancre- 3 million islets are required for successful engraftment in an aticoduodenal arteries and the common bile duct from injury during allogeneic recipient, the auto-transplant recipient can achieve the course of operation.”9 Although the term had not yet been long-term, insulin independent status after engraftment of only invented, this was the first description of a duodenum-preserving 300,000 to 400,000 islets.139 The ability to recover a sufficient pancreatic head resection. quantity of islets from a sclerotic gland is dependent on the One of the authors (C.F.F.) worked at the University of degree of disease present, however, so the selection of patients as Michigan with Gardner Child III, and performed the 95% distal candidates for autologous islet transplantation is important. Un- pancreatectomy independently. The Michigan experience with 77 fortunately, 25% to 30% of patients with chronic pancreatitis are such operations was reported at the American Surgical Association already diabetic so islet auto-transplantation is not an option in in 1976.150 Pain relief was excellent and achieved in about 80% of those patients. Of those islet transplant recipients who become patients followed on average 6 years. However, the remnant of euglycemic initially, their islet cell function remains impaired, and after 2 years most require insulin.140–142 The phenomenon of progressive islet impairment therefore affects auto-transplant recipients as well as allotransplant recipients, although the function of the auto-transplanted islets appears to be more durable.143 With fewer than 10 centers currently performing islet auto-transplantation in the United States, however, the lack of access to this procedure prevents its wide-spread adoption. In addition, further studies are necessary to understand the factors which contribute to islet unresponsiveness and apoptosis after iso- lation and engraftment.

Distal Pancreatectomy In most cases of chronic pancreatitis the head of the gland is the locus of the disease and changes in the body and tail are secondary to changes in the head. In a small percentage of cases the body and tail may be the portions of the pancreas most diseased due to isolated duct stricture, pseudocyst disease, or both. For these patients with focal inﬂammatory changes localized to the body and tail, the technique of partial (40%–80%) distal pancreatectomy has been advocated.144,145 Although distal pancreatectomy is less morbid than more extensive resectional procedures, the operation leaves untreated a major portion of the gland, and is therefore associated FIGURE 7. Child’s 95 percent distal pancreatectomy. C. G. with a signiﬁcant risk of symptomatic recurrence. It has been a more Child and A. J. Donovan described the subtotal, duodenum- popular surgery in British centers, where its success seems to be preserving distal pancreatectomy in 1956. They estimated greater, perhaps due to the lower incidence of alcoholic chronic that 5% of the pancreas was preserved adjacent to the duo- pancreatitis.146 Long-term outcomes reveal good pain relief in only denum (Reprinted with permission from Frey CF. Distal sub- 60% of patients, however, with completion pancreatectomy required total pancreatectomy. In: Malt RA. Surgical Techniques Illus- for pain relief in 13% of patients.147 trated. Philadelphia, PA: WB Saunders; 1985:421).

pancreas was insufficient to maintain glucose homeostasis and the the rim of surrounding pancreas, or by choledochojejunostomy to incidence of postoperative diabetes following 95% pancreatectomy the Roux limb of jejunum that is used to form the pancreaticojeju- rose to an unacceptable 72%. Exocrine insufficiency deteriorated as nostomy with the pancreatic body. Reconstruction consists of an well, and postoperative complications were common. Forty percent end-to-end pancreaticojejunostomy to the distal pancreas, and end- of patients experienced abscesses or short-lived fistulas in the region to-side pancreaticojejunostomy to the remnant of pancreatic tissue of the head resection. In this same 1976 report, the experience with on the inner aspect of the duodenum. The body and tail of the 19 patients who had undergone pancreaticoduodenectomy and 53 pancreas can be drained with a longitudinal pancreaticojejunostomy patients with 40% to 80% distal resections for chronic pancreatitis if the main duct in the body and tail of the pancreas is obstructed. was reviewed as well. Pain relief after pancreaticoduodenectomy Beger decompresses the common duct in about 50% of his patients was equivalent to that provided with the 95% pancreatectomy and employs the longitudinal pancreaticojejunostomy in 10% to without the high incidence of endocrine dysfunction, which con- 15% of cases.153 firmed that the head of the pancreas was the locus of the pain The operation was brilliant in its conception; it not only problem in most patients with chronic pancreatitis. relieved pain in 80% or more of patients,153–155 but preserved the body and tail of the pancreas which preserved endocrine and HYBRID PROCEDURES exocrine function. Exocrine and endocrine insufficiency after DP- Duodenum-Preserving Pancreatic Head Resection PHR progresses as a function of the underlying chronic pancreatitis and its course appears minimally altered by the operation.153,155 The In Germany in the early 1970s, a surgeon scientist at the Free incidence of new diabetes after the DPPHR procedure ranges from University of Berlin named Hans Beger had observed that many 8% to 21%, and some patients show an improvement in glucose patients with chronic pancreatitis had an inflammatory mass in the 155 head of the pancreas. He studied the blood supply to the uncinate metabolism after the procedure. This appears to be due to preservation of insulin and pancreatic polypeptide (PP) secretion process and duodenum in animals and developed a hypothesis for 74 the preservation of the ampullary region while excising the central postoperatively. The DPPHR or Beger procedure is now used portion of the pancreatic head. In 1972 he performed his first widely throughout the world. In randomized controlled trials, the duodenum-preserving pancreatic head resection, or DPPHR (Fig. 8). DPPHR or Beger procedure is equivalent or superior to other operations; pain relief occurs in 80% to 85% of all operated patients Not until he had performed 52 DPPHR procedures did he publish his 16,17 description of the surgery and results in 1980.151 In 1997, the results and is well maintained at 5 years. of 380 DPPHR operations were reviewed.152 Key steps in the performance of the DPPHR include identi- Complications fying and preserving the posterior branch of the gastroduodenal The principal complication of the DPPHR procedure is the artery which provides blood flow to the duodenum, intrapancreatic risk of ischemia of the duodenum due to inadequate perfusion of, or common bile duct, and pancreaticoduodenal groove. The neck of the failure to preserve, the posterior branch of the gastroduodenal artery. pancreas overlying the portal and superior mesenteric vein is di- In addition, the risk of leak from either of the 2 pancreaticojejunal vided, and all but a small amount of pancreatic tissue along the inner anastomoses, and the risks of delayed gastric emptying, ileus, and aspect of the duodenum is resected. The common bile duct is intra-abdominal problems are similar to that of the Whipple proce- decompressed, if necessary, either by choledochopancreatostomy to dure. In a prospective study in which 40 patients were randomized

FIGURE 8. The duodenum-preserving pancreatic head resection (DPPHR) of HG Beger. A, The neck of the pancreas is divided, and most of the head is resected sparing the distal common bile duct and duodenum. B, C, D, End-to-end and side-to-side anastomoses are constructed to the same Roux-en-Y limb of jejunum (Reprinted with permission from Bell RH Jr. Atlas of pancreatic surgery. In: Bell RH Jr, Rikkers LF, Mulholland MW. Digestive Tract Surgery. A Text and Atlas. Philadelphia, PA: Lippincott Raven; 1996:1014–1015).

FIGURE 9. LR-LPJ of Frey. In 1987, C F Frey and G J Smith described the local resection of the head of the pancreas and longitudinal pancreatico-jejunostomy. The critical contribution was the excavation of the central portion of the pancreatic head as well as complete decompression of the dorsal duct (Reprinted with permission from Bell RH Jr, Rikkers LF, Mulhol- land MW. Digestive Tract Surgery. A Text and Atlas. Philadelphia, PA: Lippincott Raven; 1996: 1014–1015). to either the DPPHR or the pylorus-preserving Whipple procedure, Buchler et al reported that postoperative morbidity (15%–20%) and length of stay (13–14 days) were similar.16 The retrospective study of Aspelund et al of various pancreatic head resections performed consecutively at Yale revealed a major complication rate after Whipple procedures of 40%, compared with 25% after the DPPHR, with the rate of leak being 10% and 25%, respectively.114

Local Resection of the Pancreatic Head With Longitudinal Pancreaticojejunostomy In 1987 a new operation for the management of pain and the complications of chronic pancreatitis was described by Frey and Smith.156 This operation was called a local resection of the pancreatic head combined with longitudinal pancreaticojejunostomy, or LR-LPJ (Fig. 9). The local resection of the head was conceived as a direct result of the author’s experience performing Child’s 95% distal pancreatectomy. Child preserved the rim of pancreatic tissue to assure an adequate blood supply to the duodenum. In the LR-LPJ FIGURE 10. Excavation of the pancreatic head including the the rim of pancreatic tissue of the entire head is preserved, and is ducts of Wirsung and Santorini, in continuity with the used to sew to the opened jejunum. The ducts of Wirsung and opened dorsal duct. Note the mucosal inflammation of the Santorini are excised, and the excavation is created in continuity obstructed duct. (Reprinted with permission from Arch Surg. with the longitudinal dochotomy of the dorsal duct. 2004;139:375–379). Key steps in the performance of the LR-LPJ include preservation of the pancreatic neck as well as the capsule of the posterior pancreatic head. In the pancreaticoduodenectomy and the DPPHR, anastomosis to a Roux-en-Y jejunal limb has proven exceptionally the pancreatic neck is freed up from the portal and superior mesen- durable with no reported leaks. teric vein confluence and divided. In the LR-LPJ, the neck of the pancreas is preserved intact as are the body and tail of the pancreas. Technical Variations Not having to divide the pancreatic neck, as in the pancreaticoduo- Subsequent to Frey’s own modification of the technique, denectomy or DPPHR, reduces the risk of the operation, as it avoids other surgeons have described modifications of the extent or tech- intraoperative problems with the venous structures lying posterior to nique of the LR-LPJ. Andersen and Topazian advocated performing the gland. To reduce the risk of penetrating the posterior capsule of the LR-LPJ as it was originally described, but alternately excising, the head, Frey and Amikura later recommended that the posterior rather than decompressing, the ducts of Wirsung and Unicate in the limit of resection be the back wall of the opened duct of Wirsung head (Fig. 10), and advocated the use of the ultrasonic aspirator and and duct to the uncinate.54 All intervening and overlying tissue in dissector for this purpose.157 The use of this device permits precise the pancreatic head including the duct of Santorini is excised. The removal of the ducts and adjacent tissue with good visualization and locally excised head of the pancreas is covered with the opened without complications.75 There is little pancreatic tissue behind these Roux-en-Y limb of jejunum in continuity with the opened main ducts and the pancreatic capsule is continuously palpated as the dissec- pancreatic duct in the body and tail of the pancreas. This side-to-side tion proceeds to ensure a safe margin of resection. The intrapancreatic

portion of the common bile duct is usually exposed, and avoiding injury to it is enhanced by the ultrasonic aspirator. The majority of the parenchyma of the uncinate process is spared, and the excavation of the pancreatic head is made contiguous with a generous dochotomy of the dorsal duct. Whether merely unroofing as opposed to removal of the proximal ducts contributes to better pain relief is not known and awaits a randomized trial to compare the 2 versions of the LR-LPJ. Izbicki et al at the University of Hamburg also recommend a more extensive excavation of the pancreatic head, and employ a technique which they refer to as the “Hamburg modification” of the LR-LPJ158 (Fig. 11). This wider excavation of the pancreatic head is created in continuity with the dorsal dochotomy, and is followed by a single, side-to-side pancreaticojejunostomy. In 2001, Ho and Frey subsequently described merely exca- FIGURE 12. Excavation of the pancreatic head without lon- vating the core of the pancreatic head, and draining the excavation gitudinal pancreaticojejunostomy. Frey’s modification of his with a Roux-en-Y pancreaticojejunostomy, but without any effort to LR-LPJ in which only the head of the pancreas is excavated include the dorsal duct159,160: (Fig. 12). In 2003, Farkas et al when the main duct is normal in size and inflammation is described a similar excavation of the central portion of the pancre- largely confined to the head of the gland (Reprinted with atic head without any effort to include the duct of the body in the permission from Arch Surg. 2001;136:1353–1358). lateral pancreaticojejunostomy,161 and reported excellent results of what they termed an “organ-preserving pancreatic head resection” or OPPHR, in a randomized comparison to the pylorus-preserving pancreaticoduodenectomy.162 This approach was advocated by Gloor et al in Bern as an alternative to the DPPHR procedure in patients with portal hypertension,163 and was described as the “Berne modification of the DPPHR” (Fig. 13). Most recently, Buchler’s group in Heidelberg has published a randomized, controlled trial of the “Berne” version of the excavation method compared with the “classic” Beger procedure.164 Operative times and length of stay were shorter in the group undergoing excavation of the pancreatic head, while long- term outcomes and quality-of-life scores were identical over 2 years postoperatively. The common element of these variations on the theme of LR-LPJ remains the excavation or “coring out” of the central portion of the pancreatic head. It remains uncertain, however, whether and to what degree the dochotomy needs to be extended into the body and tail. Puestow and Gillesby’s great contribution was the demon-

FIGURE 13. Berne Modification of the DPPHR. In 2001, Gloor et al described a method of excavation of the central portion of the pancreatic head without division of the pancreatic neck as a modification of the DPPHR (Reprinted with permission from Dig Surg. 2001;18:21–25).

stration that adequate decompression of the obstructed gland prevents subsequent restricturing and reobstruction of the diseased pancreatic duct. This accepted principle would seem at odds with the observations that the end-to-end pancreaticojejunal anastomosis of the PPPD and the excavation-only variations of Frey, Farkas, and Gloor have a low incidence of distal duct stricture. In the absence of any prospective, randomized trials to answer FIGURE 11. The Hamburg Modification of the LR-LPJ. Izbicki this question, we conclude that if the duct is uninﬂammed and described a wider version of the “coring out” of the pancre- modest in size, the dochotomy and anastomosis probably should be atic head, in which the central portion of the uncinate pro- carried only to the point where the duct diameter is no more than 3 cess is included in the excavation in continuity with a long to 4 mm. If the duct is large and the mucosa of the duct obviously dochotomy of the dorsal duct (Reprinted with permission inﬂamed (Fig. 10), a long longitudinal pancreaticojejunostomy is from Izbicki. Ibid. 2007:1310). appropriate to prevent recurrent stricture.

A common bile duct stricture, if present, should be relieved from a single or multi-institutional study. Retrospective, cohort by decompression into the same Roux limb through a separate based studies are regarded as Level 2 data by the Strength of choledochojejunostomy. Performing a choledochopancreatostomy Recommendation Taxonomy criteria. into the excavated pancreatic head has been associated with late recurrences of bile duct strictures.165 Finally, pseudocysts can be excavated in continuity with the pancreatic head excision, or can be Initial Outcomes drained into the same Roux limb of jejunum. To date, 6 published Level 1 studies have examined various comparisons between these 3 operations, and 1 Level 2 study has Complications examined all 3 procedures at a single institution (Table 1). In the Level 1 study of 43 patients by Klempa et al,154 DPPHR patients had Initial and long-term results of the LR-LPJ demonstrate pain a shorter hospital stay, greater weight gain, less post operative relief which is equivalent to that of pancreaticoduodenectomy and diabetes, and exocrine dysfunction than standard Whipple patients the DPPHR.17,166,167 The observed mortality rate has thus far been over a 3- to 5-year follow-up. Pain control was similar between the zero, and therefore less than with the Whipple procedure. Major 2 procedures. This was conﬁrmed in a Level 1 study of 40 patients complications were less with the LR-LPJ (16%) than with pancre- by Buchler et al16 in which DPPHR patients reported better pain aticoduodenectomy (40%) or DPPHR (25%) in 1 single-site series, relief, glucose tolerance, and weight gain compared with PPPD and the incidence of new postoperative diabetes after LR-LPJ was patients, however, the follow-up averaged less than 1 year. 8% with an average follow-up of 3 years.114 In a Level 1 study of 61 patients randomized to PPPD or LR-LPJ, Izbicki et al166 found a lower postoperative complication COMPARISONS OF THE 3 OPERATIVE rate associated with the Frey Procedure (19%) compared with the PROCEDURES: PANCREATICODUODENECTOMY, PPPD group (53%), and better global quality of life scores (71% vs. DPPHR (BEGER PROCEDURE), AND LR-LPJ (FREY 43%, respectively). Both operations were equally effective in con- PROCEDURE) trolling pain over a 2-year follow-up. More recently, the Level 1 There has been considerable interest particularly in European study by Farkas et al162 examined 40 patients randomized to PPPD centers to apply evidence-based methods to the study of the 3 or the method of excavation of the pancreatic head that their group operations currently advocated for the treatment of chronic pancre- described as an “organ-preserving pancreatic head resection” (OP- atitis. Reports of results of a single operative procedure from a single PHR), and found that OPPHR was associated with a shorter oper- institution are difﬁcult to compare with those of another operative ating time, less post operative morbidity, shorter hospital stay, and procedure from another institution, as patient selection, patient better quality of life than PPPD. The degree of pain relief was equal populations, measurements of pain and quality of life may vary, as overa1to3year follow-up. Operation times have been shown to be do the methods and details of follow-up. The best studies, or Level shorter with the LR-LPJ and DPPHR compared with the PPPD, and 1 data by the Strength of Recommendation Taxonomy, are prospec- intraoperative blood loss and perioperative transfusion requirements tive, randomized controlled trials comparing 2 or more operations are less with LR-LPJ and DPPHR procedures.114,164,167,168

TABLE 1. Short-Term (1–4 Year) Outcomes After Surgical Treatment of Chronic Pancreatitis Level I Studies Operative Perioperative Pain New EXO Weight Reference Mortality Morbidity Leak LOS Relief* DM† Def‡ Gain QOL§ RTW First Author Number Procedure N (%) (%) (%) (d) (%) (%) (5) (kg) Score (%) Klempa 154 DPPHR 22 1 54 0 16 100 12 20 6.4 82 — WHIP 21 0 51 5 22 70 38 100 4.9 67 — Buchler 16 DPPHR 20 0 15 0 13 94 — 100 4.1 — — PPPD 20 0 20 5 14 77 — 100 1.9 — — Izbicki 166 LR-LPJ 31 3 19 3 — 80 0 58 6.7 86 — PPPD 30 0 53 7 — 75 10 83 1.9 57 — Farkas 162 OPPHR 20 0 0 — 8 100 0 — 7.8 — 78 PPPD 20 0 40 — 14 100 15 — 3.2 — 65 Izbicki 167 DPPHR 20 0 20 5 — 70 0 50 6.7 86 70 LR-LPJ 22 0 9 0 — 70 0 50 6.4 86 68 Kroninger 164 DPPHR 32 0 20 7 15 — — — — 66 — OPPHR* 33 0 21 3 11 — — — — 71 — Level II Studies

Aspelund 114 DPPHR 12 0 25 25 10 92 8 — — — 92 LR-LPJ 12 0 16 0 11 83 8 — — — 75 PPPD 30 6 40 10 12 90 25 — — — 83 168 DPPHR 42 — — 57 26 75 — — Reidiger LR-LPJ 50 — — — — — PPPD 89 — 38 14 57 22 66 — — —

*Rellief scored as completely relieved or mostly relieved of pain; †DM, diabetes mellitus; ‡EXO, defexocrine deﬁciency; §QOL, quality of life.

TABLE 2. Long-Term (7–10 yr) Outcomes for Surgical Treatment of Chronic Pancreatitis (Level 1 Studies) Reference Pain Relief Late Mortality Diabetes Exocrine Insufﬁciency Changes in QOL Return to Work First Author Number Procedure N (%) (%) (%) (%) (%) (%) Klempa 154 DPPHR 22 100 5 25 20 — 75 WHIP 21 70 5 20 100 — 50 Izbicki 166 LR-LPJ 31 90 3 29 58 71 68 PPPD 30 87 0 37 83 43 43 Strate 172 LR-LPJ 31 82 20 61 86 58 40 PPPD 30 81 13 65 96 50 36

DPPHR indicates duodenum-preserving pancreatic head resection; WHIP, standard Whipple procedure; PPPD, pylorus-preserving pancreaticoduodenectomy; LR-LPJ, local resection of pancreatic head with longitudinal pancreaticojejunostomy; OPPHR, organ-preserving pancreatic head excavation without pancreaticojejunostomy; DM, diabetes mellitus; QOL, quality of life; Mort, mortality.

Late Morbidity and Mortality CHOICE OF OPERATION IN PEDIATRIC PATIENTS In 1995, Izbicki et al began a Level 1 study of 42 patients Pediatric patients with chronic pancreatitis due to congenital randomized to the DPPHR or LR-LPJ.167 The study was continued ductal abnormalities or hereditary pancreatitis comprise a special and updated in 1997169 to include 74 patients. In 2005 the long term subset of patients for whom the choice of operation is difficult. The results of these 74 patients with an average follow-up of 8.5 years number of pediatric patients undergoing operation for pancreatic was reported.17 There were no significant differences between the disease is relatively small, so few large series have been published groups with regard to global quality of life, pain scores, late on which to base surgical decisions or make comparison of out- mortality, exocrine or endocrine insufficiency. The Level 1 study by comes. In general, decompressive operations are favored over re- Koninger et al which compared the classic DPPHR with excavation sectional procedures, as surgical conservatism prevails in the pedi- of the pancreatic head showed identical outcomes at 2 years, after an atric age groups. In the 3 largest series of surgical treatment of initial reduction in morbidity associated with the excavation proce- pediatric cases published since 2000, less than 1 patient per year dure.164 These results were echoed in the Level 2 study by Aspe- underwent surgery for chronic pancreatitis at large referral cen- lund et al, which demonstrated fewer complications with both the ters.173–175 In the majority of cases, a Puestow-type procedure has DPPHR and LR-LPJ procedures compared with pancreaticoduo- been used, although recurrence of symptoms has resulted in the use denectomy, a lower incidence of new diabetes (8%) for both of the LR-LPJ as a “rescue” procedure in some cases.168,169 This has DPPHR and LR-LPJ compared with the Whipple procedure led some authors to conclude that the LR-LPJ is the preferred (25%), but no significant differences in outcomes or pain relief procedure for pediatric patients, with generally excellent out- between DPPHR and LR-LPJ.114 Finally, Level 2 data support comes.168 As more pediatric surgeons gain experience with the the efficacy of both DPPHR and LR-LPJ in patients with dilated technique for performing the LR-LPJ, further comparisons of out- 170,171 as well as nondilated ducts. comes will clarify the long-term benefits and morbidity of these Long-term exocrine and/or endocrine insufficiency in chronic procedures, and the effect, if any, of a combined resectional decom- pancreatitis patients treated surgically is a product of the surgical pressive procedure on the subsequent incidence of pancreatic carci- 135 intervention as well as the progression of the underlying disease. noma in children with hereditary pancreatitis. Although the short-term (3 year) incidence of new diabetes after operation appears less with the LR-LPJ and DPPHR than with the 16,114,167 PPPD, the late incidence of diabetes appears similar in all SUMMARY groups (Table 2). In a nonrandomized series of 224 patients with CP By virtue of being drained by the 3 major ductal systems of followed for a median of 5 years after PPPD (50%), DPPHR (18%), Wirsung, Uncinate, and Santorini and their tributaries, the head of or LR-LPJ (20%), there were no operation-specific trends in the 28% the pancreas is the locus of the disease in the overwhelming majority of patients who developed postoperative diabetes.168 Two-thirds of patients were found to have exocrine insufficiency long-term, which of patients with chronic pancreatitis, regardless of the etiology of the was 2-fold greater than the rate seen preoperatively. There was no disease. Pancreaticoduodenectomy, the DPPHR, and the LR-LPJ significant difference in the occurrence of exocrine dysfunction procedures all produce long lasting pain relief in about 80% of between the operations. Late (10 year) mortality occurred in one- patients with chronic pancreatitis because they all address disease in third of patients (who were, on average, 44 years old at the time of the head of the pancreas. The combined elements of decompression operation) but was rarely due to metabolic causes. Ten percent of of the distal pancreas and excision of the core of the pancreatic head deaths were due to pancreatic cancer, in the two-thirds of patients are essential for successful long-term symptom relief in this disease. whose cause of death was known. Similar findings were recently The extent of the longitudinal dochotomy appears less important reported in the randomized trial of LR-LPJ and pylorus-preserving than the excision of the central portion of the head of the gland. pancreaticoduodenectomy outcomes performed by Izbicki’s Excavation techniques are safer than techniques which require group.172 After an average of 7 years of follow-up after LR-LPJ or division of the neck of the pancreas, and are easier to perform. The PPPD, survival, pain relief, and pancreatic function were similar in early postoperative mortality and morbidity risk is highest with both groups. The rate of diabetes was slightly lower after LR-LPJ pancreaticoduodenectomy and lowest with the LR-LPJ procedure. (61%) than after PPPD (65%), but these had both more than doubled Late results are nearly identical after the 3 procedures. from their preoperative status. Therefore, we conclude that although the limited pancreatic procedures of DPPHR and LR-LPJ have a lower initial rate of endocrine dysfunction, the long-term risk of ACKNOWLEDGMENT diabetes is more related to the progression of the underlying disease The authors thank Robyn Hinke for assistance with prepara- than to the effects of operation. tion of the manuscript.

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