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Toward zero pancreatic fistula after pancreaticoduodenectomy with pancreaticogastrostomy
The American Journal of Surgery 191 (2006) 733–734
Editorial comment
Toward zero pancreatic fistula after pancreaticoduodenectomy with pancreaticogastrostomy F. Charles Brunicardi, M.D., F.A.C.S.*, William E. Fisher, M.D., F.A.C.S. Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 1709 Dryden, Suite 1500, Houston, TX 77030, USA Manuscript received January 10, 2006; revised manuscript January 18, 2006
The mortality rate after pancreatic resection has decreased in recent years, but the morbidity of the operation still remains significant. The decrease in mortality rate is likely secondary to improvements in and standardization of patient selection, operative technique, and perioperative care in large specialty centers. Pancreatic fistula is a notorious complication specific to pancreatic surgery that has been difficult to eliminate, and it occurs in 10% to 20% of patients in most series depending on the definition used. It has been assumed that pancreatic fistulas are one of the most important causes of both morbidity and mortality after pancreaticoduodenectomy. In this article, the investigators examined the morbidity of this operation in a large series of patients in whom pancreatic fistula was minimized. Overall morbidity remained significant: One third of patients suffered complications. Analysis of the complications indicated that hemorrhage, intra-abdominal fluid collection, delayed gastric emptying, and sepsis continue to be a major source of morbidity despite the fact that all of these complications were thought to be, at least in many cases, related to the development of a pancreatic fistula. The incidence of pancreatic fistula after pancreatic surgery is highly dependent on the definition used. Unfortunately, as the investigators pointed out, the definitions used in the literature vary so widely that accurate comparison between studies becomes difficult [1,2]. Recently, an international panel of pancreatic surgeons, working in wellknown, high-volume centers, developed a simple, objective, reliable, and easily applied definition of postoperative pancreatic fistula, graded primarily on clinical impact [3]. An all-inclusive definition is a drain output of any measurable volume of fluid on or after postoperative day 3 with an amylase content ⬎3 times the serum amylase activity. Three
* Corresponding author. Tel.: ⫹1-713-798-8070; fax: ⫹1-713-7986609.
different grades of pancreatic fistula were defined (A, B, and C) according to increasing clinical impact. Grade A was a transient leak with no clinical impact. Grade B required an adjustment in the clinical pathway such as keeping the patient on nothing-by-mouth status and providing parenteral nutrition, antibiotics, or somatostatin analogs. Grade C fistulas required major changes in clinical management, prolong the hospital stay, and can be life-threatening. In this study, the investigators reported a zero incidence of pancreatic fistula, but they routinely placed drains near the pancreatic anastomosis to manage early postoperative drainage. The definition of pancreatic leak used in this analysis was ⬎50 mL fluid with an amylase concentration ⬎3-fold the normal upper limit in serum on or after postoperative day 10. A repeat analysis of the data with the newer consensus definition would likely result in some grade A or even some grade B fistulas because these patients were usually discharged without delay. The question may remain, however, whether some of these apparently clinically silent pancreatic leaks are actually responsible for some of the observed complications. For decades, surgeons have searched for ways to minimize the incidence of pancreatic leak and its presumed associated morbidity after pancreatic resection. Prophylactic administration of octreotide after surgery has been studied in numerous prospective randomized trials. Some studies have demonstrated a decrease in the incidence of pancreatic fistula, and most have shown a decrease in postoperative complication rate but no change in mortality [4 – 8]. Others have shown no effect on the incidence of pancreatic fistula or complications [9 –11]. Various types of glue or biologic sealants have been used to either intentionally occlude the pancreatic duct or to seal the anastomosis and prevent pancreatic fistula, but data are too scant to reach any conclusions [12,13]. Different anastomotic techniques have been examined, including duct-to-mucosa and intussuscepted techniques for pancreaticojejunostomy and
0002-9610/06/$ – see front matter © 2006 Excerpta Medica Inc. All rights reserved. doi:10.1016/j.amjsurg.2006.01.051
734
F.C. Brunicardi and W.E. Fisher / The American Journal of Surgery 191 (2006) 733–734
pancreaticogastrostomy. An often-quoted randomized prospective trial from the United States comparing pancreaticojejunostomy with pancreaticogastrostomy demonstrated no difference in the incidence of pancreatic fistula (approximately 12% in each group) using the definition adopted by the investigators of the present article [14]. This well-designed study has probably lessened interest among some surgeons in adopting pancreaticogastrostomy as their preferred technique for the pancreatic anastomosis. However, before dismissing pancreaticogastrostomy, the current series of 194 patients demonstrating no clinically significant pancreatic fistulas should perhaps open our minds once again to considering the potential merits of this technique. It is interesting to note that complications previously attributed to a pancreatic fistula remain a significant source of morbidity in this series of pancreatic resections without clinically significant pancreatic fistula. Multivariate analysis has suggested that an American Society of Anesthesiologists (ASA) score of 3 was an independent risk factor. This has been defined by the ASA as a patient with “severe” systemic disease that is not “incapacitating.” Most patients undergoing pancreaticoduodenectomy for pancreatic cancer are in the seventh to eight decade of life, and the majority of these patients are categorized as ASA 3 in our institution compared with only approximately 11% in the current study. If the ASA score is to be used as a patient-selection factor, it will be important to assure that this somewhat vague definition is applied in a similar fashion across institutions. More than half of the patients in the current study received a blood transfusion, and this was also determined to be an independent risk factor for complications. Other institutions observe a more strict policy for blood transfusion. Certainly, the careful selection of fit patients, as well as the avoidance of intraoperative blood loss and the need for transfusion, will decrease the occurrence of complications.
References [1] Savarese L, Balestracci T, Sbrana F, et al. Histopathologic alterations of pancreatic slice after glandular section with the harmonic scalpel (Ultacision®). J Pancreas 2001;2(suppl 5):353–54. [2] Bassi C, Butturni G, Molinari E, et al. Pancreatic fistula rate after pancreatic resection. The importance of definitions. Dig Surg 2004;21:54–9. [3] Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery 2005;138:8 –13. [4] Buchler M, Friess H, Klempa I, et al. Role of octreotide in the prevention of postoperative complications following pancreatic resection. Am J Surg 1992;163:125–31. [5] Friess H, Beger HG, Sulkowski U, et al. Randomized controlled multicentre study of the prevention of complications by octreotide in patients undergoing surgery for chronic pancreatitis. Br J Surg 1995;82:1270–3. [6] Pederzoli P, Bassi C, Falconi N, et al. Efficacy of octreotide in the prevention of complications of elective pancreatic surgery. Italian Study Group. Br J Surg 1994;81:265–9. [7] Montorsi M, Zago M, Mosca F, et al. Efficacy of octreotide in the prevention of pancreatic fistula after elective pancreatic resections: a prospective, controlled, randomized clinical trial. Surgery 1995;117–31. [8] Lowy AM, Lee JE, Pisters PW, et al. Prospective, randomized trial of octreotide to prevent pancreatic fistula after pancreaticoduodenectomy for malignant disease. Ann Surg 1997;226:632– 41. [9] Yeo CJ, Cameron JL, Lillemoe KD, et al. Does prophylactic octreotide decrease the rates of pancreatic fistula and other complications after pancreaticoduodenectomy? Results of a prospective randomized placebo-controlled trial. Ann Surg 2000;232:419 –29. [10] Barnett SP, Hodul PJ, Creech S, et al. Octreotide does not prevent postoperative pancreatic fistula or mortality following pancreaticoduodenectomy. Am Surg 2004;70:222– 6. [11] Sarr MG, Pancreatic Surgery Group. The potent somatostatin analogue vapreotide does not decrease pancreas-specific complications after elective pancreatectomy: a prospective, multicenter, double-blinded, randomized, placebo-controlled trial. J Am Coll Surg 2003;196:556 – 64. [12] D’Andrea AA, Costantino V, Sperti C, et al. Human fibrin sealant in pancreatic surgery: is it useful in preventing fistulas? A prospective randomized study. Ital J Gastroenterol 1994;26:283– 6. [13] Kram HB, Clark SR, Ocampo HP, et al. Fibrin glue sealing of pancreatic injuries, resections, and anastomosis. Am J Surg 1991;161:479 – 81. [14] Yeo CJ, Cameron JL, Maher MM, et al. A prospective randomized trial of pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy. Ann Surg 1995;222:580 –92.
Editorial comment
Toward zero pancreatic fistula after pancreaticoduodenectomy with pancreaticogastrostomy F. Charles Brunicardi, M.D., F.A.C.S.*, William E. Fisher, M.D., F.A.C.S. Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 1709 Dryden, Suite 1500, Houston, TX 77030, USA Manuscript received January 10, 2006; revised manuscript January 18, 2006
The mortality rate after pancreatic resection has decreased in recent years, but the morbidity of the operation still remains significant. The decrease in mortality rate is likely secondary to improvements in and standardization of patient selection, operative technique, and perioperative care in large specialty centers. Pancreatic fistula is a notorious complication specific to pancreatic surgery that has been difficult to eliminate, and it occurs in 10% to 20% of patients in most series depending on the definition used. It has been assumed that pancreatic fistulas are one of the most important causes of both morbidity and mortality after pancreaticoduodenectomy. In this article, the investigators examined the morbidity of this operation in a large series of patients in whom pancreatic fistula was minimized. Overall morbidity remained significant: One third of patients suffered complications. Analysis of the complications indicated that hemorrhage, intra-abdominal fluid collection, delayed gastric emptying, and sepsis continue to be a major source of morbidity despite the fact that all of these complications were thought to be, at least in many cases, related to the development of a pancreatic fistula. The incidence of pancreatic fistula after pancreatic surgery is highly dependent on the definition used. Unfortunately, as the investigators pointed out, the definitions used in the literature vary so widely that accurate comparison between studies becomes difficult [1,2]. Recently, an international panel of pancreatic surgeons, working in wellknown, high-volume centers, developed a simple, objective, reliable, and easily applied definition of postoperative pancreatic fistula, graded primarily on clinical impact [3]. An all-inclusive definition is a drain output of any measurable volume of fluid on or after postoperative day 3 with an amylase content ⬎3 times the serum amylase activity. Three
* Corresponding author. Tel.: ⫹1-713-798-8070; fax: ⫹1-713-7986609.
different grades of pancreatic fistula were defined (A, B, and C) according to increasing clinical impact. Grade A was a transient leak with no clinical impact. Grade B required an adjustment in the clinical pathway such as keeping the patient on nothing-by-mouth status and providing parenteral nutrition, antibiotics, or somatostatin analogs. Grade C fistulas required major changes in clinical management, prolong the hospital stay, and can be life-threatening. In this study, the investigators reported a zero incidence of pancreatic fistula, but they routinely placed drains near the pancreatic anastomosis to manage early postoperative drainage. The definition of pancreatic leak used in this analysis was ⬎50 mL fluid with an amylase concentration ⬎3-fold the normal upper limit in serum on or after postoperative day 10. A repeat analysis of the data with the newer consensus definition would likely result in some grade A or even some grade B fistulas because these patients were usually discharged without delay. The question may remain, however, whether some of these apparently clinically silent pancreatic leaks are actually responsible for some of the observed complications. For decades, surgeons have searched for ways to minimize the incidence of pancreatic leak and its presumed associated morbidity after pancreatic resection. Prophylactic administration of octreotide after surgery has been studied in numerous prospective randomized trials. Some studies have demonstrated a decrease in the incidence of pancreatic fistula, and most have shown a decrease in postoperative complication rate but no change in mortality [4 – 8]. Others have shown no effect on the incidence of pancreatic fistula or complications [9 –11]. Various types of glue or biologic sealants have been used to either intentionally occlude the pancreatic duct or to seal the anastomosis and prevent pancreatic fistula, but data are too scant to reach any conclusions [12,13]. Different anastomotic techniques have been examined, including duct-to-mucosa and intussuscepted techniques for pancreaticojejunostomy and
0002-9610/06/$ – see front matter © 2006 Excerpta Medica Inc. All rights reserved. doi:10.1016/j.amjsurg.2006.01.051
734
F.C. Brunicardi and W.E. Fisher / The American Journal of Surgery 191 (2006) 733–734
pancreaticogastrostomy. An often-quoted randomized prospective trial from the United States comparing pancreaticojejunostomy with pancreaticogastrostomy demonstrated no difference in the incidence of pancreatic fistula (approximately 12% in each group) using the definition adopted by the investigators of the present article [14]. This well-designed study has probably lessened interest among some surgeons in adopting pancreaticogastrostomy as their preferred technique for the pancreatic anastomosis. However, before dismissing pancreaticogastrostomy, the current series of 194 patients demonstrating no clinically significant pancreatic fistulas should perhaps open our minds once again to considering the potential merits of this technique. It is interesting to note that complications previously attributed to a pancreatic fistula remain a significant source of morbidity in this series of pancreatic resections without clinically significant pancreatic fistula. Multivariate analysis has suggested that an American Society of Anesthesiologists (ASA) score of 3 was an independent risk factor. This has been defined by the ASA as a patient with “severe” systemic disease that is not “incapacitating.” Most patients undergoing pancreaticoduodenectomy for pancreatic cancer are in the seventh to eight decade of life, and the majority of these patients are categorized as ASA 3 in our institution compared with only approximately 11% in the current study. If the ASA score is to be used as a patient-selection factor, it will be important to assure that this somewhat vague definition is applied in a similar fashion across institutions. More than half of the patients in the current study received a blood transfusion, and this was also determined to be an independent risk factor for complications. Other institutions observe a more strict policy for blood transfusion. Certainly, the careful selection of fit patients, as well as the avoidance of intraoperative blood loss and the need for transfusion, will decrease the occurrence of complications.
References [1] Savarese L, Balestracci T, Sbrana F, et al. Histopathologic alterations of pancreatic slice after glandular section with the harmonic scalpel (Ultacision®). J Pancreas 2001;2(suppl 5):353–54. [2] Bassi C, Butturni G, Molinari E, et al. Pancreatic fistula rate after pancreatic resection. The importance of definitions. Dig Surg 2004;21:54–9. [3] Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery 2005;138:8 –13. [4] Buchler M, Friess H, Klempa I, et al. Role of octreotide in the prevention of postoperative complications following pancreatic resection. Am J Surg 1992;163:125–31. [5] Friess H, Beger HG, Sulkowski U, et al. Randomized controlled multicentre study of the prevention of complications by octreotide in patients undergoing surgery for chronic pancreatitis. Br J Surg 1995;82:1270–3. [6] Pederzoli P, Bassi C, Falconi N, et al. Efficacy of octreotide in the prevention of complications of elective pancreatic surgery. Italian Study Group. Br J Surg 1994;81:265–9. [7] Montorsi M, Zago M, Mosca F, et al. Efficacy of octreotide in the prevention of pancreatic fistula after elective pancreatic resections: a prospective, controlled, randomized clinical trial. Surgery 1995;117–31. [8] Lowy AM, Lee JE, Pisters PW, et al. Prospective, randomized trial of octreotide to prevent pancreatic fistula after pancreaticoduodenectomy for malignant disease. Ann Surg 1997;226:632– 41. [9] Yeo CJ, Cameron JL, Lillemoe KD, et al. Does prophylactic octreotide decrease the rates of pancreatic fistula and other complications after pancreaticoduodenectomy? Results of a prospective randomized placebo-controlled trial. Ann Surg 2000;232:419 –29. [10] Barnett SP, Hodul PJ, Creech S, et al. Octreotide does not prevent postoperative pancreatic fistula or mortality following pancreaticoduodenectomy. Am Surg 2004;70:222– 6. [11] Sarr MG, Pancreatic Surgery Group. The potent somatostatin analogue vapreotide does not decrease pancreas-specific complications after elective pancreatectomy: a prospective, multicenter, double-blinded, randomized, placebo-controlled trial. J Am Coll Surg 2003;196:556 – 64. [12] D’Andrea AA, Costantino V, Sperti C, et al. Human fibrin sealant in pancreatic surgery: is it useful in preventing fistulas? A prospective randomized study. Ital J Gastroenterol 1994;26:283– 6. [13] Kram HB, Clark SR, Ocampo HP, et al. Fibrin glue sealing of pancreatic injuries, resections, and anastomosis. Am J Surg 1991;161:479 – 81. [14] Yeo CJ, Cameron JL, Maher MM, et al. A prospective randomized trial of pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy. Ann Surg 1995;222:580 –92.