Resection Versus Drainage in Treatment of Chronic Pancreatitis

Abstract

See “Resection vs drainage in treatment of chronic pancreatitis: long-term results of a randomized trial” by Strate et al, on page 1406. See “Resection vs drainage in treatment of chronic pancreatitis: long-term results of a randomized trial” by Strate et al, on page 1406. Chronic pancreatitis is characterized by progressive fibrosis, loss of both exocrine and endocrine cells, and, in many cases, intraductal stone formation by calcification of protein precipitates. The clinical consequences may include exocrine and endocrine failure, fibrotic obstruction of structures passing through or beside the pancreatic substance (pancreatic ducts, bile duct, duodenum, splenic–portal–mesenteric veins), and very often severe pain. That pain can be intermittent, exacerbated during acute flares of inflammation, and in some cases it may abate, presumably as the gland “burns out” and fails.1Amman R.W. Muellhaupt B. The natural history of pain in alcoholic chronic pancreatitis.Gastroenterology. 1999; 116: 1132-1140Abstract Full Text Full Text PDF PubMed Scopus (314) Google Scholar The causes of pain from chronic pancreatitis remain incompletely known,2Warshaw A.L. Banks P.A. Fernández-Del Castillo C. AGA technical review: treatment of pain in chronic pancreatitis.Gastroenterology. 1998; 115: 765-776Abstract Full Text Full Text PDF PubMed Scopus (267) Google Scholar but probably include some combination of pancreatic duct obstruction and parenchymal hypertension,3Malfertheiner P. Büchler M. Correlation of imaging and function in chronic pancreatitis.Radiol Clin North Am. 1989; 27: 51-64PubMed Google Scholar injury to and encasement of sensory nerves,4Bockman D.E. Buchler M. Malfertheiner P. et al.Analysis of nerves in chronic pancreatitis.Gastroenterology. 1988; 94: 1459-1469PubMed Google Scholar and inflammation.5Di Sebastiano P. Fink T. Weihe E. et al.Immune cell infiltration and growth-associated protein 43 expression correlate with pain in chronic pancreatitis.Gastroenterology. 1997; 112: 1648-1655Abstract Full Text PDF PubMed Scopus (158) Google Scholar The latter may lead to disproportionate enlargement of the pancreatic head—the so-called inflammatory tumor—which has been noted and become a focus of surgical tactics, particularly in Germany.6Friess H. Müller M. Ebert M. et al.Chronic pancreatitis with inflammatory enlargement of the pancreatic head.Zentralbl Chir. 1995; 120: 292-297PubMed Google Scholar It is of interest that the inflammatory mass is not a universal finding of chronic pancreatitis: A study in progress (unpublished data) at the Massachusetts General Hospital (USA) and the University of Freiburg (Germany) has found that the median diameter of the pancreatic head in chronic pancreatitis is 2.6 cm among American patients and 4.5 cm among the Germans (P < .001). The difference is real but unexplained. Medical (noninterventional) treatments, which include abstinence, pancreatic enzymes, and anti-inflammatory drugs, are mostly ineffective. Approximately one half of patients with pain owing to chronic pancreatitis come to an intervention aimed principally at pain relief, along with relief of bile duct, duodenal, and major venous obstruction.7Tringali A. Boskoski I. Costamagna G. The role of endoscopy in the therapy of chronic pancreatitis.Best Pract Res Clin Gastroenterol. 2008; 22: 145-165Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar, 8Di Sebastiano P. di Mola F.F. Bockman D.E. et al.Chronic pancreatitis: the perspective of pain generation by neuroimmune interaction.Gut. 2003; 52: 907-911Crossref PubMed Scopus (99) Google Scholar, 9Cunha J.E. Penteado S. Jukemura J. et al.Surgical and interventional treatment of chronic pancreatitis.Pancreatology. 2004; 4: 540-550Abstract Full Text PDF PubMed Scopus (18) Google Scholar, 10Rattner D.W. Warshaw A.L. Venous, biliary, and duodenal obstruction in chronic pancreatitis.Hepatogastroenterology. 1990; 37: 301-306PubMed Google Scholar Although an argument for nonoperative management to await the spontaneous resolution of pain by pancreatic “burn-out,”11Ammann R.W. Diagnosis and management of chronic pancreatitis: current knowledge.Swiss Med Wkly. 2006; 136: 166-174PubMed Google Scholar that hoped-for outcome never comes, even after many years, in at least half of the patients,12Lankisch P.G. Löhr-Happe A. Otto J. et al.Natural course in chronic pancreatitis Pain, exocrine and endocrine pancreatic insufficiency and prognosis of the disease.Digestion. 1993; 54: 148-155Crossref PubMed Scopus (409) Google Scholar and the wait may be intolerable and unjustifiable when more effective therapy exists.13Warshaw A.L. Pain in chronic pancreatitis Patients, patience, and the impatient surgeon.Gastroenterology. 1984; 86: 987-989PubMed Google Scholar The surgical strategy most often is based on decompression of intrapancreatic hypertension. Historically, this has been accomplished by lateral pancreaticojejunostomy like the modified Puestow procedure,14Partington P.F. Chronic pancreatitis treated by Roux type jejunal anastomosis to the biliary tract.AMA Arch Surg. 1952; 65: 532-542Crossref PubMed Scopus (9) Google Scholar pseudocyst drainage, or caudal drainage.15Duval Jr, M.K. Caudal pancreaticojejunostomy for chronic pancreatitis; operative criteria and technique.Surg Clin North Am. 1956; : 831-839PubMed Google Scholar Experience with the pancreatic duct drainage procedures, however, has been somewhat disappointing in that initial pain relief may approach 80%, but falls off within a few years to <60%.16Markowitz J.S. Rattner D.W. Warshaw A.L. Failure of symptomatic relief after pancreaticojejunal decompression for chronic pancreatitis Strategies for salvage.Arch Surg. 1994; 129: 374-379Crossref PubMed Scopus (117) Google Scholar, 17Warshaw A.L. Popp Jr, J.W. Schapiro R.H. Long-term patency, pancreatic function, and pain relief after lateral pancreaticojejunostomy for chronic pancreatitis.Gastroenterology. 1980; 79: 289-293PubMed Google Scholar These operations also require a substantially dilated pancreatic duct (>7 mm) to be applicable, and <25% of patients are thereby eligible. Thus, there has been increasing utilization of pancreaticoduodenectomy, which provides a combination of resection of the pancreatic head, pancreatic duct decompression, relief of obstructed bile duct and duodenum, and ablation of pancreatic sensory nerves concentrated in that region.18Grace P.A. Pitt H.A. Longmire W.P. Pylorus preserving pancreatoduodenectomy: an overview.Br J Surg. 1990; 77: 968-974Crossref PubMed Scopus (175) Google Scholar Pancreaticoduodenectomy, whether performed as a traditional “Whipple” with antrectomy19Jimenez R.E. Fernandez-del Castillo C. Rattner D.W. et al.Outcome of pancreaticoduodenectomy with pylorus preservation or with antrectomy in the treatment of chronic pancreatitis.Ann Surg. 2000; 231: 293-300Crossref PubMed Scopus (219) Google Scholar or with pylorus preservation20Jimenez R.E. Fernandez-Del Castillo C. Rattner D.W. et al.Pylorus-preserving pancreaticoduodenectomy in the treatment of chronic pancreatitis.World J Surg. 2003; 27: 1211-1216Crossref PubMed Scopus (57) Google Scholar (Figure 1) is reported to achieve lasting pain relief in about 80% of patients. Pancreaticoduodenectomy also provides the benefit of a potential cure for an unrecognized pancreatic adenocarcinoma, which may arise more frequently in a bed of chronic pancreatitis.21Talamini G. Falconi M. Bassi C. et al.Incidence of cancer in the course of chronic pancreatitis.Am J Gastroenterol. 1999; 94: 1253-1260Crossref PubMed Scopus (180) Google Scholar Today, pancreaticoduodenectomy in experienced hands can usually be accomplished without the need for blood transfusion or postoperative intensive care and with an operative mortality of 2–5%.22Birkmeyer J.D. Siewers A.E. Finlayson E.V. et al.Hospital volume and surgical mortality in the United States.N Engl J Med. 2002; 346: 1128-1137Crossref PubMed Scopus (4020) Google Scholar, 23Buchler M.W. Wagner M. Schmied B.M. et al.Changes in morbidity after pancreatic resection: toward the end of completion pancreatectomy.Arch Surg. 2003; 138: 1310-1314Crossref PubMed Scopus (492) Google Scholar More recently, there has been a surge of interest in the duodenum-preserving pancreatic head resection (DPPHR) originally described by Beger et al,24Beger H.G. Witte C. Krautzberger W. et al.Experiences with duodenum-sparing pancreas head resection in chronic pancreatitis.Chirurgie. 1980; 51: 303-307Google Scholar in which the pancreatic head is cored out and a Roux-en-Y loop of jejunum is used to restore continuity for pancreatic and biliary secretions. Although the concept was rooted in the observation of a pancreatic inflammatory head mass, the operation is nonetheless applicable to any pancreas. Several modifications such as the Frey or Berne procedures have been described (Figure 1). Advocates of the DPPHR claim its advantages include greater safety and lesser functional impairment of the pancreas with equal or better pain relief.25Klempa I. Spatny M. Menzel J. et al.Pancreatic function and quality of life after resection of the head of the pancreas in chronic pancreatitis.A prospective, randomized comparative study after duodenum preserving resection of the head of the pancreas versus Whipple's operation Chirurg. 1995; 66: 350-359Google Scholar, 26Büchler M.W. Friess H. Müller M.W. et al.Randomized trial of duodenum-preserving pancreatic head resection versus pylorus-preserving Whipple in chronic pancreatitis.Am J Surg. 1995; 169: 65-69Abstract Full Text PDF PubMed Scopus (401) Google Scholar An additional advantage is that the DPPHR can often be accomplished even in the face of portal hypertension owing to mesenteric–portal vein obstruction,27Adam U. Makowiec F. Riediger H. et al.Pancreatic head resection for chronic pancreatitis in patients with extrahepatic generalized portal hypertension.Surgery. 2004; 135: 411-418Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar whereas pancreaticoduodenectomy may be impossible or risk life-threatening hemorrhage. Since 1990, there have been a number of randomized controlled trials comparing pancreaticoduodenectomy (with or without pylorus and antrum preservation) and variations of the DPPHR (Table 1). These studies, all with relatively short-term follow-up, emphasize in particular that the duodenum-preserving operations achieve rough parity in pain relief but with a lower subsequent incidence of diabetes,28Beger H.G. Schlosser W. Friess H.M. et al.Duodenum-preserving head resection in chronic pancreatitis changes the natural course of the disease: a single-center 26-year experience.Ann Surg. 1999; 230: 512-519Crossref PubMed Scopus (253) Google Scholar possibly owing to a duodenal influence on hormone secretion.29Eddes E.H. Masclee A.A. Gielkens H.A. et al.Cholecystokinin secretion in patients with chronic pancreatitis and after different types of pancreatic surgery.Pancreas. 1999; 19: 119-125Crossref PubMed Scopus (11) Google ScholarTable 1Comparative Studies of Different Pancreatic Head ResectionsStudyProceduresKlempa (1995)25Klempa I. Spatny M. Menzel J. et al.Pancreatic function and quality of life after resection of the head of the pancreas in chronic pancreatitis.A prospective, randomized comparative study after duodenum preserving resection of the head of the pancreas versus Whipple's operation Chirurg. 1995; 66: 350-359Google ScholarClassic Whipple vs. BegerBüchler (1995)26Büchler M.W. Friess H. Müller M.W. et al.Randomized trial of duodenum-preserving pancreatic head resection versus pylorus-preserving Whipple in chronic pancreatitis.Am J Surg. 1995; 169: 65-69Abstract Full Text PDF PubMed Scopus (401) Google ScholarPylorus-preserving Whipple vs. BegerMüller (2008)32Müller M.W. Friess H. Martin D.J. et al.Long-term follow-up of a randomized clinical trial comparing Beger with pylorus-preserving Whipple procedure for chronic pancreatitis.Br J Surg. 2008; 95: 350-356Crossref PubMed Scopus (92) Google ScholarPylorus-preserving Whipple vs. BegerIzbicki (1998)36Izbicki J.R. Bloechle C. Broering D.C. et al.Extended drainage versus resection in surgery for chronic pancreatitis: a prospective randomized trial comparing the longitudinal pancreaticojejunostomy combined with local pancreatic head excision with the pylorus-preserving pancreatoduodenectomy.Ann Surg. 1998; 228: 771-779Crossref PubMed Scopus (302) Google ScholarPylorus-preserving Whipple vs. FreyIzbicki (1995)37Izbicki J.R. Bloechle C. Knoefel W.T. et al.Duodenum-preserving resection of the head of the pancreas in chronic pancreatitis A prospective, randomized trial.Ann Surg. 1995; 221: 350-358Crossref PubMed Scopus (289) Google ScholarFrey vs. BegerStrate (2005)30Strate T. Bachmann K. Busch P. et al.Resection vs drainage in treatment of chronic pancreatitis: long-term results of a randomized trial.Gastroenterology. 2008; 134: 1406-1411Abstract Full Text Full Text PDF PubMed Scopus (128) Google ScholarFrey vs. Beger Open table in a new tab In this issue of Gastroenterology, Strate et al30Strate T. Bachmann K. Busch P. et al.Resection vs drainage in treatment of chronic pancreatitis: long-term results of a randomized trial.Gastroenterology. 2008; 134: 1406-1411Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar present the 7-year follow-up of their previously reported31Strate T. Taherpour Z. Bloechle C. et al.Long-term follow-up of a randomized trial comparing the Berger and Frey procedures for patients suffering from chronic pancreatitis.Ann Surg. 2005; 241: 591-598Crossref PubMed Scopus (162) Google Scholar randomized controlled trial that compared the pylorus-preserving pancreaticoduodenectomy with the Frey version of the DPPHR. Recently, a similar study published the long-term outcomes of a randomized controlled trial comparing the pylorus-preserving pancreaticoduodenectomy with the original Beger operation.32Müller M.W. Friess H. Martin D.J. et al.Long-term follow-up of a randomized clinical trial comparing Beger with pylorus-preserving Whipple procedure for chronic pancreatitis.Br J Surg. 2008; 95: 350-356Crossref PubMed Scopus (92) Google Scholar Both reports detail equivalent effectiveness with regard to pain relief, quality of life, and exocrine/endocrine functional status. Specifically, Strate et al30Strate T. Bachmann K. Busch P. et al.Resection vs drainage in treatment of chronic pancreatitis: long-term results of a randomized trial.Gastroenterology. 2008; 134: 1406-1411Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar followed 60 patients (30 after pancreaticoduodenectomy and 30 after DPPHR) and found no significant differences in any of these indices. The early functional advantages of the DPPHR were lost during longer observation and time for the disease to follow its natural progression toward deteriorating function: Diabetes was now present in 65% after pancreaticoduodenectomy and 61% after DPPHR; exocrine insufficiency (steatorrhea) occurred in 96% and 86%, respectively (P = NS). Somewhat in contrast with prior reports of excess deaths in the natural history of patients with chronic pancreatitis,28Beger H.G. Schlosser W. Friess H.M. et al.Duodenum-preserving head resection in chronic pancreatitis changes the natural course of the disease: a single-center 26-year experience.Ann Surg. 1999; 230: 512-519Crossref PubMed Scopus (253) Google Scholar the mortality was surprisingly low, at 15% in both groups, and most deaths were not pancreatic disease related. What should we learn from these reports? First and most important, pancreatic head resection, whether by pancreaticoduodenectomy or DPPHR, provides effective, lasting relief of pain and quality of life in chronic pancreatitis. Furthermore, 2 randomized controlled trials comparing surgical with endoscopic treatment,33Díte P. Ruzicka M. Zboril V. et al.A prospective, randomized trial comparing endoscopic and surgical therapy for chronic pancreatitis.Endoscopy. 2003; 35: 553-558Crossref PubMed Scopus (399) Google Scholar, 34Cahen D.L. Gouma D.J. Nio Y. et al.Endoscopic versus surgical drainage of the pancreatic duct in chronic pancreatitis.N Engl J Med. 2007; 356: 676-684Crossref PubMed Scopus (541) Google Scholar both found that the surgical procedure provided superior pain relief. Second, the method of pancreatic head resection ultimately makes little difference in the eventual outcome, although a recent meta-analysis35Diener M.K. Rahbari N.N. Fischer L. et al.Duodenum-preserving pancreatic head resection versus pancreatoduodenectomy for surgical treatment of chronic pancreatitis—a systematic review and meta-analysis.Ann Surg. 2008; (In press)PubMed Google Scholar found that the DPPHR procedures seemed to be somewhat easier to perform and to incur a lesser risk. At the end of the day, experienced surgeons are justified in choosing the surgical tactic with which they are most comfortable. Third, none of these interventions succeeds in interrupting the progression of chronic pancreatitis toward endocrine and exocrine failure. The relief of parenchymal hypertension may contribute to pain relief, but the cellular damage continues, perhaps unabated. Thus, there is still a need for replacement therapy. Oral pancreatic enzymes adequately control exocrine needs, but islet cell transplantation might be a major step forward for management of diabetes when it can be effectively accomplished. Still unanswered are the questions of diagnosis of early “minimal-change chronic pancreatitis,” the separation of somatic pain from opioid addiction, and the objective quantitation of pain sufficient to warrant a surgical treatment. Although evidence-based experience now exists to indicate what operation(s) to do and how to do it safely, the criteria for when and if to operate remain subject to the conflicting biases of surgeons, gastroenterologists, and other physicians. Resection vs Drainage in Treatment of Chronic Pancreatitis: Long-term Results of a Randomized TrialGastroenterologyVol. 134Issue 5PreviewBackground & Aims: Tailored organ-sparing procedures have been shown to alleviate pain and are potentially superior in terms of preservation of endocrine and exocrine function as compared with standard resection (Whipple) for chronic pancreatitis with inflammatory pancreatic head tumor. Long-term results comparing these 2 procedures have not been published so far. The aim of this study was to report on long-term results of a randomized trial comparing a classical resective procedure (pylorus-preserving Whipple) with an extended drainage procedure (Frey) for chronic pancreatitis. Full-Text PDF