Incapacitating pain of chronic pancreatitis: a surgical perspective of what is known and what needs to be known

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1 Incapacitating pain of chronic pancreatitis: a surgical perspective of what is known and what needs to be known Michael G. Sarr, MD, George H. Sakorafas, MD Rochester, Minnesota In a select population of patients with established chronic pancreatitis, incapacitating, overwhelming, truly intractable pain develops that markedly alters quality of life and prevents ability to function productively in society (i.e., maintain employment or homemaking duties). Attempts to control the pain by pharmacologic means, such as oral pancreatic enzymes, nonnarcotic analgesics, psychopharmacologic agents, or celiac plexus blocks may prove untenable, leading to a vicious circle of ever-increasing needs for narcotic analgesics and the secondary physical and psychosocial problems of chemical addiction. Although the role of the surgeon is to treat the complications of chronic pancreatitis (i.e., hemorrhage; GI, biliary, or vascular obstruction; selected patients with pseudocyst disease; and severe pain), this article will focus specifically on surgical approaches in the patient with incapacitating, medically intractable pain from chronic pancreatitis. Three unique situations will be addressed: (1) small duct chronic pancreatitis (main pancreatic ductal diameter <5 mm), (2) large duct chronic pancreatitis (main duct diameter >7 mm), and (3) inflammatory mass in the head of the gland. Discussion will center on controversies in anatomic and nonanatomic parenchymal resections (pancreatectomy), ductal drainage/gland decompression procedures, and selective neurotomies (greater splanchnic neurotomy) or chemical neuroablative procedures (celiac plexus blocks). The outline will address what is known, what is not known, and our opinion about which studies are needed. From the Department of Surgery, Mayo Clinic, Rochester, Minnesota. Reprints not available from author. Gastrointest Endosc 1999;49:S85-9. Copyright 1999 by the American Society for Gastrointestinal Endoscopy /99/$ /0/95817 WHAT IS KNOWN (AND HOW GOOD IS THAT WHICH IS KNOWN ) In general, pancreatic surgeons have classically based their approach to the patient with chronic pain according to (1) the presence or absence of pancreatic ductal dilatation (large duct disease equated to duct drainage with pancreaticojejunostomy, whereas small duct disease required resection) and (2) the presence of an inflammatory mass in the head of the gland that necessitated resection (Table 1). As with many dictums in medicine, some of the classic dictums became subject to change as evidence-based medicine has developed. In general, until the last 5 to 10 years, most of the classic surgical series were retrospective or nonrandomized single institutional experiences (Table 2). For large duct disease management by the Partington- Rochelle (modified Puestow) procedure 1 led to good early results of 85% to 90% relief of pain. Reliable long-term results ( 5 years) are more difficult to come by, but those available suggest a falloff in success rates to ~60% to 70% maintenance of relief of pancreatic pain. Although not perfect, unlike major pancreatic resections, primary ductal drainage preserves pancreatic parenchyma and in theory serves to maintain whatever presurgical endocrineexocrine function existed; 1 group 2,3 has even maintained that ductal drainage may improve digestion and prevent further deterioration of pancreatic function. For small duct disease, results are more difficult to interpret (Table 2). In the pre-1985 era (data not shown in Table 2), surgical emphasis and thus the resective philosophy was based on the belief that the degree or amount of pancreatic pain was proportional to the amount of parenchyma involved. In general, distal subtotal resections were performed from the tail toward the head of the gland 60% to 80% to 95% resections. 4 These distal-based resections avoided the need for pancreaticoduodenectomy, which required duodenectomy and a biliaryenteric anastomosis, which in that era carried formidable operative morbidity and potential mortality. Although early results seemed encouraging, interest in left-to-right sided resections waned because of poor long-term results, not only in pain relief but also because of the resultant pancreatic exocrine and especially endocrine insufficiency induced surgically by the 80% to 95% resections; moreover, this patient population was often composed of noncompliant alcoholics. VOLUME 49, NO. 3, PART 2, 1999 GASTROINTESTINAL ENDOSCOPY S85

2 M Sarr, G Sakorafas Incapacitating pain of chronic pancreatitis: surgical perspective Table 1. Classical surgical approach to incapacitating pain of chronic pancreatitis Small duct disease Inflammatory mass in head of gland Ductal drainage Pancreatic resection (a) Pre-1985 era: distal pancreatectomy (60%-95%) (b) Post-1985 era: proximal pancreatectomy (pancreatoduodenectomy) Proximal pancreatectomy (a) Pancreatoduodenectomy (b) Nonanatomic duodenum-preserving head resection Table 2. Selected* surgical series of managing intractable pain of chronic pancreatitis Relief of pain Ductal anatomy/investigator Definition of pain relief Short-term ( 2 y) Long-term ( 5 y) Ductal drainage procedures 1974 Leger et al. 27 Good Brinton et al. 28 Good Bradley 29 Good to fair Mannell et al. 30 Relief Greenlee et al. 31 Complete or substantial 80 Small duct disease Parenchymal resection 1974 Leger et al. 27 Good or fair Frey et al. 32 Alive, working Rossi et al. 33 Complete improvement Stone et al. 6 Complete, partial but significant Howard and Zhang 34 Good to excellent Traverso and Kozarek 5 Pain free 76 Not available Ductal drainage 1974 Leger et al. 27 Good Delcore et al. 10 Completely free of pain 85 Not available 1998 Izbicki et al. 9 Complete relief of symptoms 90 Not available 1998 Rios et al. 8 Better 25 Not available Inflammatory mass in head of gland (resection) 1994 Frey and Amikura 18 Excellent Izbicki et al. 16 Pain free or infrequent episodes 95 Not available 1998 Buchler et al. 15 No pain or rare occurrence Not available *The authors apologize to those surgical investigators whose reported experience was not included in this table. Every attempt was made to give a broad overview of the field. The concept of the pacemaker of the pain of chronic pancreatitis residing in the head of the gland, generally attributed to Longmire at the University of California, Los Angeles, 5 stimulated interest in the post-1985 era in proximal pancreatectomy. Markedly improved operative mortalities of <5% after pancreatoduodenectomy, probably the result of improved support services and expanded experience with resections for malignancy, further encouraged the surgical focus to center on proximal resections. Short-term results (<2 years) were generally quite good with 70% to 80% significant relief of pain. Reports of long-term results (>5 years) are less common, but as with large duct disease, results generally fall off a bit to 50% to 70% success rates (Table 2). In an attempt to further increase success in this difficult population, several groups explored the use of total pancreatectomy, hoping that if all the pancreatic parenchyma was resected chronic pain would be relieved. 6,7 Unfortunately, results of total pancreatectomy were especially disappointing, not only in pain relief (only 40% to 80% relief) but also because of the obligate metabolic consequences of the apancreatic state. Readmissions for metabolic sequellae were all too common and frequently serious. 7 Recently, these groups have addressed an oftenasked, but never well-evaluated, question Will a primary duct drainage procedure lead to pain relief in small duct disease? Results were poor in one S86 GASTROINTESTINAL ENDOSCOPY VOLUME 49, NO. 3, PART 2, 1999

3 Incapacitating pain of chronic pancreatitis: surgical perspective M Sarr, G Sakorafas Table 3. Proposed studies to address appropriate management of intractable pain of chronic pancreatitis Anatomy Large and small duct disease (stratified) Small duct disease (without inflammatory mass in head of gland) Study groups for comparison Thoracoscopic splanchnicectomy Endoscopic chemical splanchnicectomy Pancreatic resection Pancreatoduodenectomy Duodenum-preserving, nonanatomic head resection Lateral pancreaticojejunostomy Proximal resection with or without drainage of distal remnant Drainage alone study 8 but appeared excellent in 2 other studies 9,10 ; a good explanation for such contrasting results remains unknown. The concept that the pain of chronic pancreatitis is a compartment syndrome 11 that requires unroofing of the restrictive pancreatic capsule has been used to justify this approach because intraparenchymal pressure is increased in these patients 12 and may exacerbate the changes observed in parenchymal nerves. 13 However, no good correlation was found between parenchymal pressure and pain score. 14 Nevertheless, successful results with a primary nonresectional ductal drainage and decompression procedure would be very attractive, especially in the patient with compensated but borderline pancreatic function. For patients with an inflammatory mass in the head of the gland (a small subset in the United States but apparently more frequent in Europe), proximal resection has been the procedure of choice with or without complete ductal drainage of the distal gland Results are similar to those of resection or drainage (~90% relief). A small but prospective randomized study by Izbicki et al. 15,16 suggests that the less-demanding nonanatomic resection, recently updated by Frey and Amikura, 18 is favored over the more technically difficult Beger resection. 15 Ductal drainage alone of a dilated pancreatic duct, in the presence of an inflammatory mass in the head of the gland, is technically impossible because the pancreatic duct courses posteriorly as it enters the head of the gland and requires a nonanatomic wedge-type resection of the overlying pancreatic parenchyma just to expose the duct. Criticism of the above-reported literature relates to the descriptive and often subjective nature of the definitions of success of pain relief (see Table 2, definition of pain relief). Attempts at a more objective evaluation of success with, for instance, prospectively designed visual analog scales of pain (see Lillemoe et al. 19 ) or validated quality-of-life instruments (see Izbicki et al., 9 Bloechle et al., 20 and Rios et al. 8 as examples) are largely lacking. In addition, burn out of disease would be expected to occur in some percentage (amount unknown) of the group with operation. 21 In the absence of controlled studies with patients without operations, the actual benefit of surgery remains uncertain. In addition to these criticisms, another confounding factor in evaluating success is the presence of chemical (narcotic) addiction in a large percentage of patients in most of these studies, making reliable evaluation of postoperative pain extremely difficult. Surgical denervation Recently, the explosion of minimally invasive surgical techniques has rekindled interest in surgical denervation of the pancreas. Because typical pancreatic pain is believed to be visceral (and not somatic) in origin and visceral pain should involve visceral afferent nerves (largely sympathetic in origin, i.e., the splanchnic nerves), several groups 22 have suggested use of minimally invasive thoracoscopic approaches to transection of the greater splanchnic nerve(s). Reported short-term results are almost unbelievably encouraging (~80% relief of pain) 23 ; however, again the above criticisms also apply to the majority of these studies long-term results are nonexistent and surgical memory of the extensive neurotomy applied to the pancreas in the past (see Wong et al.) 22 should be remembered as distinct failures for durable long-term relief of pain. WHAT IS NOT KNOWN Despite functionally 40 years of recent experience with pancreatic surgery for chronic pancreatitis, basic questions concerning selection of patients and therapeutic interventions remain. 1. What is the expected incidence of burn out (i.e., spontaneous regression of pain over 5 years)? 2. Does preoperative chemical (narcotic) dependence affect patient outcomes? 3. Is celiac plexus block with either a neurolyticneuroablative agent or steroids effective in relieving pain or avoiding operation? 4. Which is the best operation for large duct disease? 5. Which is the best operation for small duct dis ease? VOLUME 49, NO. 3, PART 2, 1999 GASTROINTESTINAL ENDOSCOPY S87

4 M Sarr, G Sakorafas Incapacitating pain of chronic pancreatitis: surgical perspective 6. Is a duodenum-preserving nonanatomic resection comparable to a formal pancreaticoduodenectomy? 7. Can pancreatic visceral pain be accurately differentiated from nonvisceral pain to thereby select patients for thoracoscopic splanchnic nerve transection? And what is the long-term (5-year) efficacy of this approach? POTENTIALLY IMPORTANT STUDIES With the above background in mind, what studies, if successfully designed and completed, would add important and clinically relevant information to the management of the persistent intractable pain of chronic pancreatitis? Three studies are proposed (Table 3), all of which would be markedly facilitated by a multicenter approach to maximize patient accrual as well as to allow a more universal acceptance of results across a more broad patient (and surgeon) population. The first proposed study is surgical neurotomy (thoracoscopic splanchnicectomy) versus chemical neural ablation (endoscopic celiac plexus block) versus pancreatic resection (pancreatoduodenectomy or duodenum-preserving head resection). This study could be applied to patients with large duct and small duct disease but stratified according to duct size ( 8 mm or <8 mm). This study would allow objective evaluation of efficacy of minimally invasive techniques of neuroablation that preserve the pancreatic parenchyma. Because a formal pancreatectomy in the presence of chronic pancreatitis is often difficult, there are other potentially important ramifications (social, economic) in addition to the concept of pain control. If a thoracoscopic approach is justified on the basis of positive results from this study, regionalization by referral to major centers with extensive experience with pancreatic resection, as seems warranted with pancreatic cancer, 24,25 might be avoided. The second proposed study is pancreatoduodenectomy (pylorus-preserving) versus a duodenumpreserving nonanatomic head resection versus drainage alone by pancreaticojejunostomy for small duct disease without an inflammatory mass in the head of the gland. Both the Frey and Beger procedures 15,18 were originally described for patients with inflammatory masses in the head region yet if the pacemaker of pain resides in the head region, a duodenum-preserving type of resection may prove equally successful, possibly by resecting the postganglionic nerve bundles to or from the celiac plexus. 26 Because the duodenum-preserving resections are less technically demanding, 18 referral to major centers may not be necessary if the resections are effective. Two recent studies 9,10 claiming good results with drainage alone for small duct are intriguing; if drainage (with its associated pancreatic parenchymal decompression ) provides equally good results, the threshold for suggestion of operative intervention in this group of patients may markedly (and rightfully so) decrease. The third proposed study is duct drainage alone versus proximal resection with ductal drainage of remnant (body/tail) for large duct disease. Although duct drainage provides reasonable success, pain recurs in at least 20% to 30% of patients by 5 years postoperatively. Would incorporating a resection of the pacemaker region (especially with the less demanding duodenum-preserving technique should it prove equivalent for formal anatomic resection) with a ductal drainage procedure help the subgroup that fails duct drainage alone? This study would markedly change the currently accepted approach of avoiding parenchymal resection whenever the duct is dilated and would add support to the recent report by Traverso and Kozarek 5 relating their results with pancreaticoduodenectomy for small or large duct disease. All these studies would require appropriate stratification of patient population according to the etiology of chronic pancreatitis (especially alcoholic versus nonalcoholic) and postsurgical abstinence from alcohol intake. Ideally, each study would include a control group without operation; however, in our opinion, the severity of preoperative symptoms probably precludes ethical inclusion of a noninterventional control group. How to deal with the presence of active preoperative chemical (narcotic) dependence will need to be addressed; ideally patients would undergo an intense preoperative attempt at detoxification with inpatient or well-controlled outpatient continuation of counseling for chemical dependence postoperatively. Criteria of success would require unambiguous objective scoring of intensity of chronic pain, incidence of episodic pain, and validated quality-of-life instruments. Criteria of success will require re-evaluation and follow-up at least 5 years postoperatively, not only with pain control but also with social rehabilitation. ACKNOWLEDGMENT We thank Deborah Frank for her assistance in the preparation of this manuscript. REFERENCES 1. Partington PF, Rochelle RE. Modified Puestow procedure for retrograde drainage of the pancreatic duct. Ann Surg 1960; 152: Nolan WA, Townsend CM Jr, Thompson JC. Operative drainage of the pancreatic duct delays functional impairment S88 GASTROINTESTINAL ENDOSCOPY VOLUME 49, NO. 3, PART 2, 1999

5 Incapacitating pain of chronic pancreatitis: surgical perspective M Sarr, G Sakorafas in patients with chronic pancreatitis: a prospective analysis. Ann Surg 1988;208: Nealon WH, Thompson JC. Progressive loss of pancreatic function in chronic pancreatitis is delayed by main pancreatic duct decompression: a longitudinal prospective analysis of the modified Puestow procedure. Ann Surg 1993;217: Sawyer R, Frey CF. Is there still a role for distal pancreatectomy surgery for chronic pancreatitis? Am J Surg 1994;168: Traverso LW, Kozarek RA. Pancreatoduodenectomy for chronic pancreatitis: anatomic selection criteria and subsequent long-term outcome analysis. Ann Surg 1997;226: Stone WM, Sarr MG, Nagorney DM, McIlrath DC. Chronic pancreatitis: results of Whipple resection and total pancreatectomy. Arch Surg 1988;123: Braasch JW, Vito L, Nugent FW. Total pancreatectomy for end-stage chronic pancreatitis. Ann Surg 1978;188: Rios GA, Adams DB, Yeoh K-G, Tarnasky PR, Cunningham JT, Hawes RH. Outcome of lateral pancreaticojejunostomy in the management of chronic pancreatitis with non-dilated pancreatic ducts. J Gastrointest Surg 1998;2: Izbicki JR, Bloechle C, Broerig DC, Kuechler T, Broelsch CE. Longitudinal V-shaped excision of the ventral pancreas for small duct disease in severe chronic pancreatitis: prospective evaluation of a new surgical procedure. Ann Surg 1998;227: Delcore R, Rodriguez FJ, Thomas JH, Forster J, Hermreck AS. The role of pancreatojejunostomy in patients without dilated pancreatic ducts. Am J Surg 1994;168: Karanjia ND, Widdison AL, Leung F, Alvarez C, Lutrin FJ, Reber HA. Compartment syndrome in experimental chronic obstructive pancreatitis: effect of decompressing the main pancreatic duct. Br J Surg 1994;81: Jalleh RP, Aslam M, Williamson RCN. Pancreatic tissue and ductal pressures in chronic pancreatitis. Br J Surg 1991;78: Bockman DE, Buchler M, Malfertheiner P, Beger HG. Analysis of nerves in chronic pancreatitis. Gastroenterology 1988;94: Manes G, Buchler M, Pieramico O, Sebastiano PD, Malfertheiner P. Is increased pancreatic pressure related to pain in chronic pancreatitis. Int J Pancreatol 1994;15: Buchler MW, Freiss H, Bittner R, Roscher R, Krautzberger W, Muller MW, et al. Duodenum-preserving pancreatic head resection: long-term results. J Gastrointest Surg 1997;1: Izbicki JR, Bloechle C, Knoefel WT, Kuechler T, Binmoeller KF, Broelsch CE. Duodenum-preserving resection of the head of the pancreas in chronic pancreatitis: a prospective randomized trial. Ann Surg 1995;221: Buchler MW, Friess H, Muller MW, Wheatley AM, Beger HG. Randomized trial of duodenum-preserving pancreatic head resection versus pylorus-preserving Whipple in chronic pancreatitis. Am J Surg 1995;169: Frey CF, Amikura K. Local resection of the head of the pancreas combined with longitudinal pancreaticojejunostomy in the management of patients with chronic pancreatitis. Ann Surg 1994;220: Lillemoe KD, Cameron JL, Kaufman HS, Yeo CJ, Pitt HA, Sauter PK. Chemical splanchnicectomy in patients with unresectable pancreatic cancer: a prospective randomized trial. Ann Surg 1993;217: Bloechle C, Izbicki JR, Knoefel WT, Kuechler T, Broelsch CE. Quality of life in chronic pancreatitis results after duodenum-preserving resection of the head of the pancreas. Pancreas 1995;11: Ammann RW, Akovbiantz A, Largiader F, Schueler G. Course and outcome of chronic pancreatitis: longitudinal study of a mixed medical-surgical series of 245 patients. Gastroenterology 1984;86: Wong GY, Sakorafas G, Tsiotos GG, Sarr MG. Palliation of pain in chronic pancreatitis: use of neural blocks and neurotomy. Surg Clin North Am. In press. 23. Bradley EL III, Reynhout JA, Peer GL. Thoracoscopic splanchnicectomy for small duct chronic pancreatitis: case selection by differential epidural anesthesia. J Gastrointest Surg 1998;2: Lieberman MD, Kilburn H, Lindsey M, Brennan MF. Relation of perioperative deaths to hospital volume among patients undergoing pancreatic resection for malignancy. Ann Surg 1995;222: Gordon TA, Burleyson GP, Tielsch JM, Cameron JL. The effects of regionalization on cost and outcome for one general high-risk surgical procedure. Ann Surg 1995;221: Voshioka H, Wakabayashi T. Therapeutic neurotomy on head of pancreas for relief of pain due to chronic pancreatitis. Arch Surg 1958;46: Leger L, Lenriot JP, Lemaigri G. Five to twenty years followup after surgery for chronic pancreatitis in 148 patients. Ann Surg 1974;180: Brinton MH, Pellegrini CA, Stein SF, Way LW. Surgical treatment of chronic pancreatitis. Am J Surg 1984;148: Bradley EL III. Long-term results of pancreatojejunostomy in patients with chronic pancreatitis. Am J Surg 1987;153: Mannell A, Adson MA, McIlrath DC, Ilstrup DM. Surgical management of chronic pancreatitis: long-term results in 141 patients. Br J Surg 1988;75: Greenlee HB, Prinz RA, Aranha GV. Long-term results of sideto-side pancreaticojejunostomy. World J Surg 1990;14: Frey CF, Child CG III, Fry W. Pancreatectomy for chronic pancreatitis. Ann Surg 1976;184: Rossi RL, Rothschild J, Braasch JW, Munson JL, ReMine SG. Pancreatoduodenectomy in the management of chronic pancreatitis. Arch Surg 1987;122: Howard JM, Zhang Z. Pancreaticoduodenectomy (Whipple resection) in the treatment of chronic pancreatitis. World J Surg 1990;14: VOLUME 49, NO. 3, PART 2, 1999 GASTROINTESTINAL ENDOSCOPY S89

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