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Endoscopic pancreatic sphincterotomy and stenting for preoperative prophylaxis of pancreatic fistula after distal pancreatectomy
ORIGINAL ARTICLE: Clinical Endoscopy
Endoscopic pancreatic sphincterotomy and stenting for preoperative prophylaxis of pancreatic fistula after distal pancreatectomy Bernhard Rieder, MD, Daniel Krampulz, MD, Jost Adolf, MD, Albrecht Pfeiffer, MD Memmingen, Munich, Germany
Background: Pancreatic fistula (PF) is the most common postoperative complication after distal pancreatectomy (DP). Endoscopic pancreatic sphincterotomy and drainage have been shown to be an effective treatment for PF. Recently, preoperative endoscopic pancreatic stenting was proposed to prevent PF, but there are no controlled trials so far. Objective: We investigated whether preoperative pancreatic sphincterotomy and stenting could prevent the development of PF in patients with DP. Design: Nonrandomized cohort study with a prospective endoscopic intervention group and a retrospective control group. Setting: Single-center academic teaching hospital. Patients: Preoperative endoscopic pancreatic sphincterotomy and stenting were intended to prevent PF after DP in 25 patients between July 2004 and October 2008. The incidence of PF was compared with that in a control group of 23 patients who underwent DP between January 2001 and March 2004 without preoperative endoscopic intervention. Interventions: Pancreatic sphincterotomy and stenting. Main Outcome Measurement: PF rate. Results: Overall, a cohort of 48 patients underwent DP between January 2001 and October 2008. In all 25 patients who underwent preoperative endoscopic pancreatic intervention, sphincterotomy was successfully performed, and stenting of the pancreatic duct was successful in 23 patients. PF developed in none of the 25 patients in the endoscopic intervention group. In the 23 patients without preoperative endoscopic intervention, a PF developed in 5 patients (22%) (P ⫽ .02). Limitations: Nonrandomized design, retrospective control group. Conclusions: Preoperative pancreatic sphincterotomy and stenting were a feasible and safe procedure in this series. Prophylactic preoperative endoscopic intervention may decrease PF rates after DP. (Gastrointest Endosc 2010;72:536-42.)
Surgery is required for the treatment of many malignant or benign diseases of the pancreas. The appropriate surgical procedure depends on the nature, location, and extent of the underlying disease. Distal pancreatectomy (DP) is the procedure of choice for pancreatic resections to the left of the superior mesenteric vein. DP accounts for one
fourth to one third of all pancreatic resections.1 Although the mortality rate in high-volume centers is less than 3%,2 morbidity remains considerable.3 Pancreatic fistula (PF) is the most common postoperative complication after DP, with an incidence ranging from 5% to 60%, depending on the diagnostic criteria used.1-7 There are several risk factors
Abbreviations: DP, distal pancreatectomy; PF, pancreatic fistula.
Current affiliations: II. Medical Department (B.R., A.P.), Surgical Department (D.K., J.A.), Klinikum Memmingen, Memmingen, Germany, Academic Teaching Hospital of the Ludwig-Maximilians University, Munich, Germany.
DISCLOSURE: All authors disclosed no financial relationships relevant to this publication. See CME section; p. 600
Reprint requests: Bernhard Rieder, MD, II. Medical Department, Klinikum Memmingen, Bismarckstr. 23, 87700 Memmingen, Germany.
Copyright © 2010 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 doi:10.1016/j.gie.2010.04.011
If you would like to chat with an author of this article, you may contact Dr. Rieder at [email protected].
Received December 6, 2009. Accepted April 8, 2010.
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for the development of postoperative PF reported in the literature. Some of them are patient-related factors such as age younger than 65 years,8 increased weight with a body mass index greater than 25,9,10 higher American Society of Anesthesiologists score,9 decreased albumin level,9 and impaired preoperative renal function.11 Other risk factors are procedure related such as extended lymphadenectomy,8 not ligating the main pancreatic duct,8,12 concomitant splenectomy,13 the soft texture of pancreatic parenchyma,13 or an operating time longer than 480 minutes.14 Most PFs resolve spontaneously; however, refractory postoperative PFs develop in some patients with complications such as intraperitoneal abscess, sepsis, and hemorrhage, which result in additional interventional or surgical procedures, prolonged hospital stay, and, in some cases, death. Therefore, various prophylactic strategies to prevent postoperative PFs have been implemented. Different surgical techniques for pancreatic transection and stump closure (eg, by using an ultrasonic dissector or an automatic stapler),15-17 fibrin glue sealing of the pancreatic stump,18 and perioperative octreotide administration19 have been used recently, but none of these procedures eliminates the risk of postoperative PF formation. Based on the observation that endoscopic pancreatic sphincterotomy and drainage are an effective treatment of postoperative PF,20,21 preoperative endoscopic pancreatic stenting has been proposed recently to prevent PF after DP.22 However, the benefit of preoperative endoscopic pancreatic stenting has not been demonstrated so far in a controlled trial. In this study, we investigated prospectively whether preoperative pancreatic sphincterotomy and stenting could reduce the incidence of postoperative PF after DP. The incidence of PF was compared with that of a retrospective control group of patients without preoperative endoscopic intervention.
MATERIAL AND METHODS Preoperative endoscopic pancreatic sphincterotomy and stenting were offered to all adult patients since July 2004 who were anticipated to undergo DP. Endoscopy was performed with the patient under conscious sedation by using midazolam and propofol. After cannulation of the pancreatic duct with a guidewire, pancreatic sphincterotomy was performed. Subsequently, a 5F pancreatic stent was placed over the guidewire. To minimize the risk of spontaneous stent migration, we chose a stent length that was as long as possible in each individual patient, but the stent had to be short enough so that the distal tip of the stent did not cross the transection plane; the length of the stents used ranged from 4 to 6 cm. The stent was left in place for 8 weeks postoperatively. Informed consent was obtained from every patient at least 24 hours before the endoscopic procedure. www.giejournal.org
Endoscopic pancreatic sphincterotomy and stenting
Take-home Message ●
Pancreatic fistula is the most common postoperative complication after distal pancreatectomy. In this cohort study, the authors show that pancreatic sphincterotomy and stenting were safe and feasible and prevented pancreatic fistula development after distal pancreatectomy.
All patients were scheduled for endoscopy 8 weeks postoperatively. Stent removal was performed without repeated pancreaticography. There was no systematic follow-up after stent removal. The patients in the control group underwent DP without previous endoscopic intervention. DP was performed by the same surgeon in both periods by using the same technique. According to the type and extent of the underlying condition, DP was performed as a spleen-preserving resection or combined with splenectomy. After complete mobilization of the pancreatic tail, the resection was performed by using a monopolar electrosurgical instrument. In advanced pancreatic carcinoma, DP was performed as a multivisceral en bloc resection combined with partial colectomy, partial gastrectomy, omentectomy, or adrenalectomy. In addition, vascular resection and reconstruction of the portal vessels and the celiac axis were performed in some cases. Closure of the pancreatic remnant was achieved with a separately stitched ligation of the pancreatic duct, followed by single-stitched suturing of the entire pancreatic stump. At least 1 intra-abdominal drainage tube was placed; the drainage tube was removed after the fourth postoperative day if there was no PF. Samples of drainage fluid were analyzed for amylase. Prophylactic octreotide was not administered. According to the guidelines of the International Study Group on Pancreatic Fistula, PF was defined as a drainage output of any measurable volume of fluid after the third postoperative day with an amylase level greater than 3 times the upper normal value of serum amylase.23 The International Study Group on Pancreatic Fistula Working Group proposed a grading system for the stratification of PFs: grade A (low grade) resolve spontaneously and need no intervention, grade B (medium grade) require a change in management or adjustment of the clinical pathway, but patients are not severely ill. Grade C is a refractory postoperative PF that requires a major change in clinical management and aggressive clinical intervention and is associated with systemic illness and sepsis.
Statistical analysis The primary outcome analyzed was the development of a postoperative PF. The presence of a significant difference in the incidence of PFs among the 2 groups was assessed with Volume 72, No. 3 : 2010 GASTROINTESTINAL ENDOSCOPY
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TABLE 1. Demographic data, patient-associated risk factors for postoperative pancreatic fistula development, and underlying condition of patients in the control group and stenting group Control group (n ⴝ 23)
Stenting group (n ⴝ 25)
P value
12/11
11/14
NS
Clinical data and patient-associated risk factors for postoperative PF development Sex (M/F) Age, y (range)
65 (36-84)
68 (40-81)
NS
Age ⬍65 y
48% (11/23)
36% (9/25)
NS
BMI (range)
23.5 (18-36)
23.9 (17.7-30.9)
NS
Patients with BMI ⬎25
22% (5/23)
44% (11/25)
NS
ASA score 1
4% (1/23)
16% (4/25)
NS
ASA score 2
44% (10/23)
48% (12/25)
NS
ASA score 3
48% (11/23)
32% (8/25)
NS
ASA score 4
4% (1/23)
4% (1/25)
NS
52% (12/23)
36% (9/25)
NS
Patients with ASA score ⬎2 Albumin level, g/dL (range)
3.9 (2.3-4.5)
Patients with decreased albumin (⬍3.6 g/dL)
35% (8/23)
Creatinine level, mg/dL (range)
24% (6/25)
1.0 (0.6-1.8)
Patients with impaired renal function (creatinine ⬎1.2 mg/dL)
3.9 (3.1-3.7)
0.9 (0.5-1.4)
NS NS NS
17% (4/23)
12% (3/25)
NS
Adenocarcinoma
57% (13/23)
52% (13/25)
NS
Neuroendocrine tumor
22% (5/23)
8% (2/25)
NS
Intraductal papillary mucinous tumor
4% (1/23)
8% (2/25)
NS
Cystadenoma
4% (1/23)
12% (3/25)
NS
13% (3/23)
20% (5/25)
NS
Indications for distal pancreatectomy
Focal pancreatitis or pancreatic pseudocyst
ASA, American Society of Anesthesiologists; BMI, body mass index; F, female; M, male; NS, not significant (P ⬎ .05); PF, pancreatic fistula.
univariate analysis with the Fisher exact test. Comparison of continuous variables was performed by using the MannWhitney test. Results are reported as median values, unless indicated otherwise. Statistical significance was accepted at P ⬍ .05. Statistical analyses were performed with SPSS software (SPSS, Inc, Chicago, Illinois).
RESULTS Between July 2004 and October 2008, preoperative pancreatic sphincterotomy and stenting were performed in 25 patients who were anticipated to undergo DP. The incidence of PF was compared with that of a control group of 23 patients who underwent DP between January 2001 and March 2004 without preoperative endoscopic intervention. 538 GASTROINTESTINAL ENDOSCOPY
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There was no difference between the stenting group and the control group with regard to patient-related risk factors for the development of a postoperative PF (age, body mass index, American Society of Anesthesiologists score, albumin level, renal function) and the underlying condition. The most common indication for DP was adenocarcinoma in both groups; less common indications were neuroendocrine tumors, intraductal papillary mucinous tumors, cystadenoma, and focal pancreatitis or pancreatic pseudocyst (Table 1). Endoscopic pancreatic sphincterotomy was performed in all 25 patients in the intervention group. In 2 patients, a guidewire could not be passed for more than few centimeters after cannulation of the pancreatic duct because of a sharp angulation of the duct that caused repeated side-branch entry. In these cases, sphincterotomy was performed without subsequent placement of a pancreatic stent. www.giejournal.org
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Endoscopic pancreatic sphincterotomy and stenting
One patient with an intraductal papillary mucinous tumor had mild pancreatitis after stent placement that resolved within 2 days with conservative treatment. There was no relevant bleeding and no perforation (Table 2). Eight weeks postoperatively, endoscopic stent removal was performed without repeated pancreaticography. Spontaneous stent dislocation had occurred in 5 patients. There was no difference between the stenting group and the control group regarding procedure-related risk factors for postoperative PF such as extended lymphadenectomy, splenectomy, and not ligating the main pancreatic duct. Although the median operating time was shorter in the stenting group, there was no difference regarding the number of patients with a prolonged operating time (⬎480 minutes) (Table 3). A postoperative PF developed in 5 patients in the control group who had no preoperative endoscopic intervention, corresponding to a rate of 22%. The PF resolved spontaneously in 2 of them (grade A), but 3 patients required further interventions such as percutaneous drainage, surgical revision, and therapeutic endoscopic drainage (grade B/C). These patients also had a prolonged postoperative hospital stay (Table 4).
TABLE 2. Endoscopic procedures and complications in the stenting group Stenting group (n ⴝ 25) Endoscopic procedure EPS EPS and stenting Days before surgery, no. (range)
25 23 (92%) 6 (1-18)
Complications Pancreatitis
1 (4%)
Bleeding
0
Perforation
0
EPS, Endoscopic pancreatic sphincterotomy.
Stent placement was successful in 23 patients, for a success rate of 92%. Access through the minor papilla because of a pancreas divisum was required in 1 patient. The endoscopic procedure took place within 6 days (range 1-18 days) before the planned surgical resection.
TABLE 3. Surgical procedures, procedure-related risk factors for pancreatic fistula development, and complications in the stenting group and control group Control group (n ⴝ 23)
Stenting group (n ⴝ 25)
P value
DP
6 (26%)
5 (20%)
NS
DP with splenectomy
7 (30%)
11 (44%)
NS
10 (43%)
9 (36%)
NS
Surgical procedure
DP with multivisceral resection Procedure-associated risk factors Extended lymphadenectomy Not ligating the MPD
74% (17/23) 0
72% (18/25) 0
NS NS
Splenectomy
65% (15/23)
68% (17/25)
NS
Operating time, min
255 (193-505)
205 (150-395)
.017
Patients with operating time ⬎480 min
4% (1/23)
0
NS
22% (5/23)
0
.02
PF Non-PF-related complications Intra-abdominal bleeding
4% (1/23)
4% (1/25)
NS
Pneumonia
9% (2/23)
4% (1/25)
NS
Acute coronary syndrome
0
4% (1/25)
NS
Enterocutaneous fistula
0
4% (1/25)
NS
15 (9-46)
NS
Postoperative hospital stay, days (range)
15 (8-91)
DP, Distal pancreatectomy; MPD, main pancreatic duct; NS, not significant (P ⬎ .05); PF, pancreatic fistula.
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TABLE 4. Clinical characteristics, preoperative and operative interventions, and postoperative course in patients with postoperative pancreatic fistula Patient (sex), age (y), date of surgery
Diagnosis
Preop. EPS/ stent
Surgical procedure
Output volume (mL/d)
Complication (grade)
Course (length of hospital stay)
120
None (A)
Resolved spontaneously (9 d)
R.S. (F), 65, 09/2002
NET
No
DP, SpE, AdrE
G.B. (M), 74, 03/2003
IPMT
No
DP
30
None (A)
Resolved spontaneously (15 d)
H.M. (F), 79, 03/2001
AdCA
No
DP, SpE
50
Abscess (B)
Percutaneous drainage (39 d)
H.N. (M), 61, 12/2003
PsCy
No
DP, SpE
100
Abscess, sepsis (C)
Percutaneous drainage, reoperation, EPS ⫹ stent (91 d)
E.N. (F), 67, 03/2004
AdCA
No
DP, SpE, PVseg
200
Abscess (C)
Percutaneous drainage, reoperation, EPS ⫹ stent (46 d)
AdCA, Adenocarcinoma; AdrE, adrenalectomy; DP, distal pancreatectomy; EPS, endoscopic pancreatic sphincterotomy; IPMT, intraductal papillary mucinous tumor; NET, neuroendocrine tumor; Preop, preoperative; PsCy, pseudocyst; PVseg, segmental portal vein resection; SpE, splenectomy. Grading according to the International Study Group on Pancreatic Fistula classification.23
PFs developed in none of the 25 patients in the endoscopic intervention group. The observed difference in the incidence of PFs was statistically significant with P ⫽ .02 (Fig. 1). Contrary to the significant decrease in the incidence of postoperative PFs in the stenting group, other postoperative complications occurred with a similar rate in both the control and stenting groups (Table 3).
DISCUSSION Although the mortality rate after DP decreased to less than 3% in experienced hands, the complication rate remains considerably high, even in high-volume centers.1-7 Therefore, avoiding complications after pancreatic surgery
Figure 1. Incidence of postoperative PF in the control group and the stenting group.
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is an important issue. The standard surgical technique for the closure of the pancreatic resection plane after DP is ligation of the main duct and suturing the pancreatic remnant. However, the resection plane has as many as 5 side-branch stumps that cannot all be identified and ligated during transection because of their small diameters.24 These may lead to postoperative PF development.22 Numerous strategies have been used in an attempt to reduce the PF rate, including different surgical techniques, sealing methods, and pharmacologic blocking of pancreatic secretion; however, PFs remain a clinically relevant problem.15-19,24 Preoperative pancreatic stenting in the setting of DP has been advocated based on an observational study in which no PFs were observed in 10 patients.22 Only limited data on the prevention of PFs after pancreatic resection by pancreatic duct stenting are available. In a relatively large randomized trial in patients who underwent pancreaticoduodenectomy, there was no benefit demonstrated in the stenting group, but a nonsignificant trend for a higher PF rate after intraoperative pancreatic stenting.25 In contrast, in patients with local pancreatic resection or DP (ie, in pancreatic sphincter–preserving resections), there are 2 uncontrolled case series with 5 and 10 patients, respectively, that showed no postoperative PFs after preoperative endoscopic stenting of the pancreatic duct.22,26 In another case-control study, there was a significant decrease in the postoperative PF rate and length of hospital stay in patients who underwent DP with intraoperative transampullary pancreatic duct stenting.27 To our knowledge, our study is the first controlled study that showed that preoperative endoscopic pancreatic www.giejournal.org
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sphincterotomy and stenting prevent postoperative PF development after DP. The above-mentioned studies suggest that pancreatic duct stenting is only effective in preventing postoperative PFs in pancreatic sphincter–preserving resections. The pressure gradient between the pancreatic duct and the duodenum is markedly decreased after pancreatic duct stenting.28 Therefore, the pancreatic juice flow is redirected from the pancreatic resection plane to the duodenum, allowing the site of pancreatic leakage to seal. In contrast, PFs that develop after pancreaticoduodenectomy represent a leakage of the pancreaticojejunal anastomosis, which cannot be sealed effectively by pancreatic duct stenting according to the results of Winter et al.25 Because stent dislocation after pancreatic duct stenting is common and stent occlusion may induce complications such as pancreatitis, we combined pancreatic stenting with sphincterotomy to ensure pancreatic duct decompression irrespective of the stent function. The combined success rate for pancreatic sphincterotomy and stenting was high (92%). The incidence of post-ERCP pancreatitis was estimated to be low because the risk of post-ERCP pancreatitis is decreased approximately threefold by pancreatic duct stenting.29 Indeed, early complications after stent placement were limited to 1 case of mild pancreatitis. In the 2 patients in whom stent placement failed, pancreatitis did not develop, although the risk of post-ERCP pancreatitis is increased by as much as 12.1% after pancreatic sphincterotomy without pancreatic stent placement.30 As in the study of Abe et al,31 post-ERCP pancreatitis occurred in a patient with an intraductal papillary mucinous tumor. Probably the mucin that is secreted by these tumors leads to early stent obstruction, with the risk of subsequent obstructive pancreatitis. The authors of this study concluded that preoperative stenting seems unsuitable for patients with this type of tumor. Even though the overall risk of postoperative pancreatitis seems low, preprocedure ERCP and stenting may be associated with periprocedural pancreatitis that could delay or preclude subsequent DP. We recommend stent placement for a period of 8 weeks to ensure that the resection site was healed and the patients had recovered from surgery. We are aware that stenting of the pancreatic duct can induce ductal changes that resemble the changes in chronic pancreatitis, but there seems to be no correlation of stent-induced changes with the duration of stenting.32 We did not assess by follow-up pancreatogram whether there were long-term sequelae of pancreatic stenting such as ductitis or papillary stenosis at the time of the stent removal. Another concern of long-term stenting of the pancreatic duct is stent occlusion. Ikenberry et al33 showed that the occlusion rate of pancreatic stents increased in a nearly linear fashion with the length of time that stents were left in the duct. In our patients, there were no clinically apparent cases of panwww.giejournal.org
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creatitis from stent occlusion before stent removal. The optimal duration of pancreatic stenting has yet to be defined. From an intent-to-treat standpoint, 5 patients were needed to be treated to prevent 1 PF. To prevent a PF that required a change in the clinical course (grades B and C), the number needed to treat was 8. The efficacy might be increased by risk stratification, restricting pancreatic duct stenting to patients with patient-related risk factors (age younger than 65 years,8 increased weight with a body mass index ⬎25,9,10 higher American Society of Anesthesiologists score,9 decreased albumin level,9 and impaired preoperative renal function11). In our study, all 5 patients in whom a PF developed had at least 1 patient-related risk factor. The main limitations of our study are the retrospective data capture within the control group and the singlecenter setting. Although the surgeon who performed the pancreatic resections was highly experienced at the beginning of the control period, it cannot be excluded that part of the better outcome in the endoscopic intervention group is because of an increase in experience, which might also be reflected in a shorter operating time in the stenting group. The advanced imaging techniques allow a higher detection rate and a more exact preoperative characterization, even of asymptomatic pancreatic lesions that are often located in the distal part of the pancreas. Therefore, the number of patients undergoing DP might increase in the future, making effective strategies to prevent postoperative complications even more important. In summary, although this retrospective study has potential selection biases, the findings suggest that preoperative pancreatic sphincterotomy and stenting are a feasible and safe procedure that prevented PF development after DP. Before recommending this intervention in clinical routine, a larger multicenter, randomized, prospective, controlled study is required to evaluate the benefit of this approach.
REFERENCES 1. Balcom JH 4th, Rattner DW, Warshaw AL, et al. Ten-year experience with 733 pancreatic resections: changing indications, older patients, and decreasing length of hospitalization. Arch Surg 2001;136:391-8. 2. Lillemoe KD, Kaushal S, Cameron JL, et al. Distal pancreatectomy: indication and outcome in 235 patients. Ann Surg 1999;229:693-700. 3. Büchler MW, Wagner M, Schmied BM, et al. Changes in morbidity after pancreatic resection: toward the end of completion pancreatectomy. Arch Surg 2003;138:1310-4. 4. Halloran CM, Ghaneh P, Bosonnet L, et al. Complications of pancreatic cancer resection, Dig Surg 2002;19:138-46. 5. Brennan MF, Moccia RD, Klimstra D. Management of adenocarcinoma of the body and the tail of the pancreas. Ann Surg 1996;223:506-11. 6. Sheehan MK, Beck K, Creech S, et al. Distal pancreatectomy: does the method of closure influence fistula formation? Am Surg 2002;68:264-8. 7. Fahy BN, Frey CF, Ho HS, et al. Morbidity, mortality and technical factors of distal pancreatectomy. Am J Surg 2002;183:237-41.
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Endoscopic pancreatic sphincterotomy and stenting 8. Yoshioka R, Saiura A, Koga R, et al. Risk factors for clinical pancreatic fistula after distal pancreatectomy: analysis of consecutive 100 patients. World J Surg 2010;34:121-5. 9. Goh BK, Tan YM, Chung YF, et al. Critical appraisal of 232 consecutive distal pancreatectomies with emphasis on risk factors, outcome, and management of the postoperative pancreatic fistula: a 21-year experience at a single institution. Arch Surg 2008;143:956-65. 10. Sledzianowski JF, Duffas JP, Muscari F, et al. Risk factors for mortality and intra-abdominal morbidity after distal pancreatectomy. Surgery 2005; 137:180-5. 11. Adam U, Makowiec F, Riediger H, et al. Pancreatic leakage after pancreas resection. An analysis of 345 operated patients [in German with English abstract]. Chirurg 2002;73:466-73. 12. Pannegeon V, Pessaux P, Sauvanet A, et al. Pancreatic fistula after distal pancreatectomy: predictive risk factors and value of conservative treatment. Arch Surg 2006;141:1071-6. 13. Ridolfini MP, Alfieri S, Gourgiotis S, et al. Risk factors associated with pancreatic fistula after distal pancreatectomy, which technique of pancreatic stump closure is more beneficial? World J Gastroenterol 2007;13: 5096-100. 14. Kleeff J, Diener MK, Z’graggen K, et al. Distal pancreatectomy: risk factors for surgical failure in 302 consecutive cases. Ann Surg 2007;245:573-82. 15. Suzuki Y, Fujino Y, Tanioka Y, et al. Randomized clinical trial of ultrasonic dissector or conventional division in distal pancreatectomy for nonfibrotic pancreas. Br J Surg 1999;86:608-11. 16. Takeuchi K, Tsuzuki Y, Ando T, et al. Distal pancreatectomy: is stapler closure beneficial? Aust NZ J Surg 2003;73:922-5. 17. Ferrone CR, Warshaw AL, Rattner DW, et al. Pancreatic fistula rates after 462 distal pancreatectomies: staplers do not decrease fistula rates. J Gastrointest Surg 2008;12:1691-7. 18. Suc B, Msika S, Fingerhut A, et al. Temporary fibrin glue occlusion of the main pancreatic duct in the prevention of intraabdominal complications after pancreatic resection. Ann Surg 2003;237:57-65. 19. Li-Ling J, Irving M. Somatostatin and octreotide in the prevention or postoperative pancreatic complications and the treatment of enterocutaneous pancreatic fistulas: a systematic review of randomized controlled trials. Br J Surg 2001;88:190-9. 20. Costamagna G, Mutignani M, Ingrosso M, et al. Endoscopic treatment of postsurgical external pancreatic fistulas. Endoscopy 2001;33:317-22.
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Rieder et al 21. Goasguen N, Bourrier A, Ponsot P, et al. Endoscopic management of pancreatic fistula after distal pancreatectomy and enucleation. Am J Surg 2009;197:715-20. 22. Abe N, Sugiyama M, Suzuki Y, et al. Preoperative endoscopic pancreatic stenting: a novel prophylactic measure against pancreatic fistula after distal pancreatectomy. J Hepatobiliary Pancreat Surg 2008;15:373-6. 23. Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery 2005;138:8-13. 24. Konishi T, Hiraishi M, Kubota K, et al. Segmental occlusion of the pancreatic duct with prolamine to prevent fistula formation after distal pancreatectomy. Ann Surg 1995;130:165-70. 25. Winter JM, Cameron JL, Campbell KA, et al. Does pancreatic duct stenting decrease the rate of pancreatic fistula following pancreaticoduodenectomy? Results of a prospective randomized trial. J Gastrointest Surg 2006;10:1280-90. 26. Hirota M, Kanemitsu K, Takamori H, et al. Local pancreatic resection with preoperative endoscopic transpapillary stenting. Am J Surg 2007;194: 308-10. 27. Fischer CP, Bass B, Fahy B, et al. Transampullary pancreatic duct stenting decreases pancreatic fistula rate following left pancreatectomy. Hepatogastroenterology 2008;55:244-8. 28. Renou C, Grandval P, Ville E, et al. Endoscopic treatment of the main pancreatic duct: correlations among morphology, manometry, and clinical follow-up. Int J Pancreatol 2000;27:143-9. 29. Singh P, Das A, Isenberg G, et al. Does prophylactic pancreatic stent placement reduce the risk of post-ERCP pancreatitis? A meta-analysis of controlled trials. Gastrointest Endosc 2004;60:544-50. 30. Hookey LC, RioTinto R, Delhaye M, et al. Risk factors for pancreatitis after pancreatic sphincterotomy: a review of 572 cases. Endoscopy 2006;38: 670-6. 31. Abe N, Sugiyama M, Suzuki Y, et al. Preoperative endoscopic pancreatic stenting for prophylaxis of pancreatic fistula development after distal pancreatectomy. Am J Surg 2006;191:198-200. 32. Smith MT, Sherman S, Ikenberry SO, et al. Alterations in pancreatic ductal morphology following polyethylene pancreatic stent therapy. Gastrointest Endosc 1996;44:268-75. 33. Ikenberry SO, Sherman S, Hawes RH, et al. The occlusion rate of pancreatic stents. Gastrointest Endosc 1994;40:611-3.
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Endoscopic pancreatic sphincterotomy and stenting for preoperative prophylaxis of pancreatic fistula after distal pancreatectomy Bernhard Rieder, MD, Daniel Krampulz, MD, Jost Adolf, MD, Albrecht Pfeiffer, MD Memmingen, Munich, Germany
Background: Pancreatic fistula (PF) is the most common postoperative complication after distal pancreatectomy (DP). Endoscopic pancreatic sphincterotomy and drainage have been shown to be an effective treatment for PF. Recently, preoperative endoscopic pancreatic stenting was proposed to prevent PF, but there are no controlled trials so far. Objective: We investigated whether preoperative pancreatic sphincterotomy and stenting could prevent the development of PF in patients with DP. Design: Nonrandomized cohort study with a prospective endoscopic intervention group and a retrospective control group. Setting: Single-center academic teaching hospital. Patients: Preoperative endoscopic pancreatic sphincterotomy and stenting were intended to prevent PF after DP in 25 patients between July 2004 and October 2008. The incidence of PF was compared with that in a control group of 23 patients who underwent DP between January 2001 and March 2004 without preoperative endoscopic intervention. Interventions: Pancreatic sphincterotomy and stenting. Main Outcome Measurement: PF rate. Results: Overall, a cohort of 48 patients underwent DP between January 2001 and October 2008. In all 25 patients who underwent preoperative endoscopic pancreatic intervention, sphincterotomy was successfully performed, and stenting of the pancreatic duct was successful in 23 patients. PF developed in none of the 25 patients in the endoscopic intervention group. In the 23 patients without preoperative endoscopic intervention, a PF developed in 5 patients (22%) (P ⫽ .02). Limitations: Nonrandomized design, retrospective control group. Conclusions: Preoperative pancreatic sphincterotomy and stenting were a feasible and safe procedure in this series. Prophylactic preoperative endoscopic intervention may decrease PF rates after DP. (Gastrointest Endosc 2010;72:536-42.)
Surgery is required for the treatment of many malignant or benign diseases of the pancreas. The appropriate surgical procedure depends on the nature, location, and extent of the underlying disease. Distal pancreatectomy (DP) is the procedure of choice for pancreatic resections to the left of the superior mesenteric vein. DP accounts for one
fourth to one third of all pancreatic resections.1 Although the mortality rate in high-volume centers is less than 3%,2 morbidity remains considerable.3 Pancreatic fistula (PF) is the most common postoperative complication after DP, with an incidence ranging from 5% to 60%, depending on the diagnostic criteria used.1-7 There are several risk factors
Abbreviations: DP, distal pancreatectomy; PF, pancreatic fistula.
Current affiliations: II. Medical Department (B.R., A.P.), Surgical Department (D.K., J.A.), Klinikum Memmingen, Memmingen, Germany, Academic Teaching Hospital of the Ludwig-Maximilians University, Munich, Germany.
DISCLOSURE: All authors disclosed no financial relationships relevant to this publication. See CME section; p. 600
Reprint requests: Bernhard Rieder, MD, II. Medical Department, Klinikum Memmingen, Bismarckstr. 23, 87700 Memmingen, Germany.
Copyright © 2010 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 doi:10.1016/j.gie.2010.04.011
If you would like to chat with an author of this article, you may contact Dr. Rieder at [email protected].
Received December 6, 2009. Accepted April 8, 2010.
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for the development of postoperative PF reported in the literature. Some of them are patient-related factors such as age younger than 65 years,8 increased weight with a body mass index greater than 25,9,10 higher American Society of Anesthesiologists score,9 decreased albumin level,9 and impaired preoperative renal function.11 Other risk factors are procedure related such as extended lymphadenectomy,8 not ligating the main pancreatic duct,8,12 concomitant splenectomy,13 the soft texture of pancreatic parenchyma,13 or an operating time longer than 480 minutes.14 Most PFs resolve spontaneously; however, refractory postoperative PFs develop in some patients with complications such as intraperitoneal abscess, sepsis, and hemorrhage, which result in additional interventional or surgical procedures, prolonged hospital stay, and, in some cases, death. Therefore, various prophylactic strategies to prevent postoperative PFs have been implemented. Different surgical techniques for pancreatic transection and stump closure (eg, by using an ultrasonic dissector or an automatic stapler),15-17 fibrin glue sealing of the pancreatic stump,18 and perioperative octreotide administration19 have been used recently, but none of these procedures eliminates the risk of postoperative PF formation. Based on the observation that endoscopic pancreatic sphincterotomy and drainage are an effective treatment of postoperative PF,20,21 preoperative endoscopic pancreatic stenting has been proposed recently to prevent PF after DP.22 However, the benefit of preoperative endoscopic pancreatic stenting has not been demonstrated so far in a controlled trial. In this study, we investigated prospectively whether preoperative pancreatic sphincterotomy and stenting could reduce the incidence of postoperative PF after DP. The incidence of PF was compared with that of a retrospective control group of patients without preoperative endoscopic intervention.
MATERIAL AND METHODS Preoperative endoscopic pancreatic sphincterotomy and stenting were offered to all adult patients since July 2004 who were anticipated to undergo DP. Endoscopy was performed with the patient under conscious sedation by using midazolam and propofol. After cannulation of the pancreatic duct with a guidewire, pancreatic sphincterotomy was performed. Subsequently, a 5F pancreatic stent was placed over the guidewire. To minimize the risk of spontaneous stent migration, we chose a stent length that was as long as possible in each individual patient, but the stent had to be short enough so that the distal tip of the stent did not cross the transection plane; the length of the stents used ranged from 4 to 6 cm. The stent was left in place for 8 weeks postoperatively. Informed consent was obtained from every patient at least 24 hours before the endoscopic procedure. www.giejournal.org
Endoscopic pancreatic sphincterotomy and stenting
Take-home Message ●
Pancreatic fistula is the most common postoperative complication after distal pancreatectomy. In this cohort study, the authors show that pancreatic sphincterotomy and stenting were safe and feasible and prevented pancreatic fistula development after distal pancreatectomy.
All patients were scheduled for endoscopy 8 weeks postoperatively. Stent removal was performed without repeated pancreaticography. There was no systematic follow-up after stent removal. The patients in the control group underwent DP without previous endoscopic intervention. DP was performed by the same surgeon in both periods by using the same technique. According to the type and extent of the underlying condition, DP was performed as a spleen-preserving resection or combined with splenectomy. After complete mobilization of the pancreatic tail, the resection was performed by using a monopolar electrosurgical instrument. In advanced pancreatic carcinoma, DP was performed as a multivisceral en bloc resection combined with partial colectomy, partial gastrectomy, omentectomy, or adrenalectomy. In addition, vascular resection and reconstruction of the portal vessels and the celiac axis were performed in some cases. Closure of the pancreatic remnant was achieved with a separately stitched ligation of the pancreatic duct, followed by single-stitched suturing of the entire pancreatic stump. At least 1 intra-abdominal drainage tube was placed; the drainage tube was removed after the fourth postoperative day if there was no PF. Samples of drainage fluid were analyzed for amylase. Prophylactic octreotide was not administered. According to the guidelines of the International Study Group on Pancreatic Fistula, PF was defined as a drainage output of any measurable volume of fluid after the third postoperative day with an amylase level greater than 3 times the upper normal value of serum amylase.23 The International Study Group on Pancreatic Fistula Working Group proposed a grading system for the stratification of PFs: grade A (low grade) resolve spontaneously and need no intervention, grade B (medium grade) require a change in management or adjustment of the clinical pathway, but patients are not severely ill. Grade C is a refractory postoperative PF that requires a major change in clinical management and aggressive clinical intervention and is associated with systemic illness and sepsis.
Statistical analysis The primary outcome analyzed was the development of a postoperative PF. The presence of a significant difference in the incidence of PFs among the 2 groups was assessed with Volume 72, No. 3 : 2010 GASTROINTESTINAL ENDOSCOPY
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TABLE 1. Demographic data, patient-associated risk factors for postoperative pancreatic fistula development, and underlying condition of patients in the control group and stenting group Control group (n ⴝ 23)
Stenting group (n ⴝ 25)
P value
12/11
11/14
NS
Clinical data and patient-associated risk factors for postoperative PF development Sex (M/F) Age, y (range)
65 (36-84)
68 (40-81)
NS
Age ⬍65 y
48% (11/23)
36% (9/25)
NS
BMI (range)
23.5 (18-36)
23.9 (17.7-30.9)
NS
Patients with BMI ⬎25
22% (5/23)
44% (11/25)
NS
ASA score 1
4% (1/23)
16% (4/25)
NS
ASA score 2
44% (10/23)
48% (12/25)
NS
ASA score 3
48% (11/23)
32% (8/25)
NS
ASA score 4
4% (1/23)
4% (1/25)
NS
52% (12/23)
36% (9/25)
NS
Patients with ASA score ⬎2 Albumin level, g/dL (range)
3.9 (2.3-4.5)
Patients with decreased albumin (⬍3.6 g/dL)
35% (8/23)
Creatinine level, mg/dL (range)
24% (6/25)
1.0 (0.6-1.8)
Patients with impaired renal function (creatinine ⬎1.2 mg/dL)
3.9 (3.1-3.7)
0.9 (0.5-1.4)
NS NS NS
17% (4/23)
12% (3/25)
NS
Adenocarcinoma
57% (13/23)
52% (13/25)
NS
Neuroendocrine tumor
22% (5/23)
8% (2/25)
NS
Intraductal papillary mucinous tumor
4% (1/23)
8% (2/25)
NS
Cystadenoma
4% (1/23)
12% (3/25)
NS
13% (3/23)
20% (5/25)
NS
Indications for distal pancreatectomy
Focal pancreatitis or pancreatic pseudocyst
ASA, American Society of Anesthesiologists; BMI, body mass index; F, female; M, male; NS, not significant (P ⬎ .05); PF, pancreatic fistula.
univariate analysis with the Fisher exact test. Comparison of continuous variables was performed by using the MannWhitney test. Results are reported as median values, unless indicated otherwise. Statistical significance was accepted at P ⬍ .05. Statistical analyses were performed with SPSS software (SPSS, Inc, Chicago, Illinois).
RESULTS Between July 2004 and October 2008, preoperative pancreatic sphincterotomy and stenting were performed in 25 patients who were anticipated to undergo DP. The incidence of PF was compared with that of a control group of 23 patients who underwent DP between January 2001 and March 2004 without preoperative endoscopic intervention. 538 GASTROINTESTINAL ENDOSCOPY
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There was no difference between the stenting group and the control group with regard to patient-related risk factors for the development of a postoperative PF (age, body mass index, American Society of Anesthesiologists score, albumin level, renal function) and the underlying condition. The most common indication for DP was adenocarcinoma in both groups; less common indications were neuroendocrine tumors, intraductal papillary mucinous tumors, cystadenoma, and focal pancreatitis or pancreatic pseudocyst (Table 1). Endoscopic pancreatic sphincterotomy was performed in all 25 patients in the intervention group. In 2 patients, a guidewire could not be passed for more than few centimeters after cannulation of the pancreatic duct because of a sharp angulation of the duct that caused repeated side-branch entry. In these cases, sphincterotomy was performed without subsequent placement of a pancreatic stent. www.giejournal.org
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Endoscopic pancreatic sphincterotomy and stenting
One patient with an intraductal papillary mucinous tumor had mild pancreatitis after stent placement that resolved within 2 days with conservative treatment. There was no relevant bleeding and no perforation (Table 2). Eight weeks postoperatively, endoscopic stent removal was performed without repeated pancreaticography. Spontaneous stent dislocation had occurred in 5 patients. There was no difference between the stenting group and the control group regarding procedure-related risk factors for postoperative PF such as extended lymphadenectomy, splenectomy, and not ligating the main pancreatic duct. Although the median operating time was shorter in the stenting group, there was no difference regarding the number of patients with a prolonged operating time (⬎480 minutes) (Table 3). A postoperative PF developed in 5 patients in the control group who had no preoperative endoscopic intervention, corresponding to a rate of 22%. The PF resolved spontaneously in 2 of them (grade A), but 3 patients required further interventions such as percutaneous drainage, surgical revision, and therapeutic endoscopic drainage (grade B/C). These patients also had a prolonged postoperative hospital stay (Table 4).
TABLE 2. Endoscopic procedures and complications in the stenting group Stenting group (n ⴝ 25) Endoscopic procedure EPS EPS and stenting Days before surgery, no. (range)
25 23 (92%) 6 (1-18)
Complications Pancreatitis
1 (4%)
Bleeding
0
Perforation
0
EPS, Endoscopic pancreatic sphincterotomy.
Stent placement was successful in 23 patients, for a success rate of 92%. Access through the minor papilla because of a pancreas divisum was required in 1 patient. The endoscopic procedure took place within 6 days (range 1-18 days) before the planned surgical resection.
TABLE 3. Surgical procedures, procedure-related risk factors for pancreatic fistula development, and complications in the stenting group and control group Control group (n ⴝ 23)
Stenting group (n ⴝ 25)
P value
DP
6 (26%)
5 (20%)
NS
DP with splenectomy
7 (30%)
11 (44%)
NS
10 (43%)
9 (36%)
NS
Surgical procedure
DP with multivisceral resection Procedure-associated risk factors Extended lymphadenectomy Not ligating the MPD
74% (17/23) 0
72% (18/25) 0
NS NS
Splenectomy
65% (15/23)
68% (17/25)
NS
Operating time, min
255 (193-505)
205 (150-395)
.017
Patients with operating time ⬎480 min
4% (1/23)
0
NS
22% (5/23)
0
.02
PF Non-PF-related complications Intra-abdominal bleeding
4% (1/23)
4% (1/25)
NS
Pneumonia
9% (2/23)
4% (1/25)
NS
Acute coronary syndrome
0
4% (1/25)
NS
Enterocutaneous fistula
0
4% (1/25)
NS
15 (9-46)
NS
Postoperative hospital stay, days (range)
15 (8-91)
DP, Distal pancreatectomy; MPD, main pancreatic duct; NS, not significant (P ⬎ .05); PF, pancreatic fistula.
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TABLE 4. Clinical characteristics, preoperative and operative interventions, and postoperative course in patients with postoperative pancreatic fistula Patient (sex), age (y), date of surgery
Diagnosis
Preop. EPS/ stent
Surgical procedure
Output volume (mL/d)
Complication (grade)
Course (length of hospital stay)
120
None (A)
Resolved spontaneously (9 d)
R.S. (F), 65, 09/2002
NET
No
DP, SpE, AdrE
G.B. (M), 74, 03/2003
IPMT
No
DP
30
None (A)
Resolved spontaneously (15 d)
H.M. (F), 79, 03/2001
AdCA
No
DP, SpE
50
Abscess (B)
Percutaneous drainage (39 d)
H.N. (M), 61, 12/2003
PsCy
No
DP, SpE
100
Abscess, sepsis (C)
Percutaneous drainage, reoperation, EPS ⫹ stent (91 d)
E.N. (F), 67, 03/2004
AdCA
No
DP, SpE, PVseg
200
Abscess (C)
Percutaneous drainage, reoperation, EPS ⫹ stent (46 d)
AdCA, Adenocarcinoma; AdrE, adrenalectomy; DP, distal pancreatectomy; EPS, endoscopic pancreatic sphincterotomy; IPMT, intraductal papillary mucinous tumor; NET, neuroendocrine tumor; Preop, preoperative; PsCy, pseudocyst; PVseg, segmental portal vein resection; SpE, splenectomy. Grading according to the International Study Group on Pancreatic Fistula classification.23
PFs developed in none of the 25 patients in the endoscopic intervention group. The observed difference in the incidence of PFs was statistically significant with P ⫽ .02 (Fig. 1). Contrary to the significant decrease in the incidence of postoperative PFs in the stenting group, other postoperative complications occurred with a similar rate in both the control and stenting groups (Table 3).
DISCUSSION Although the mortality rate after DP decreased to less than 3% in experienced hands, the complication rate remains considerably high, even in high-volume centers.1-7 Therefore, avoiding complications after pancreatic surgery
Figure 1. Incidence of postoperative PF in the control group and the stenting group.
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is an important issue. The standard surgical technique for the closure of the pancreatic resection plane after DP is ligation of the main duct and suturing the pancreatic remnant. However, the resection plane has as many as 5 side-branch stumps that cannot all be identified and ligated during transection because of their small diameters.24 These may lead to postoperative PF development.22 Numerous strategies have been used in an attempt to reduce the PF rate, including different surgical techniques, sealing methods, and pharmacologic blocking of pancreatic secretion; however, PFs remain a clinically relevant problem.15-19,24 Preoperative pancreatic stenting in the setting of DP has been advocated based on an observational study in which no PFs were observed in 10 patients.22 Only limited data on the prevention of PFs after pancreatic resection by pancreatic duct stenting are available. In a relatively large randomized trial in patients who underwent pancreaticoduodenectomy, there was no benefit demonstrated in the stenting group, but a nonsignificant trend for a higher PF rate after intraoperative pancreatic stenting.25 In contrast, in patients with local pancreatic resection or DP (ie, in pancreatic sphincter–preserving resections), there are 2 uncontrolled case series with 5 and 10 patients, respectively, that showed no postoperative PFs after preoperative endoscopic stenting of the pancreatic duct.22,26 In another case-control study, there was a significant decrease in the postoperative PF rate and length of hospital stay in patients who underwent DP with intraoperative transampullary pancreatic duct stenting.27 To our knowledge, our study is the first controlled study that showed that preoperative endoscopic pancreatic www.giejournal.org
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sphincterotomy and stenting prevent postoperative PF development after DP. The above-mentioned studies suggest that pancreatic duct stenting is only effective in preventing postoperative PFs in pancreatic sphincter–preserving resections. The pressure gradient between the pancreatic duct and the duodenum is markedly decreased after pancreatic duct stenting.28 Therefore, the pancreatic juice flow is redirected from the pancreatic resection plane to the duodenum, allowing the site of pancreatic leakage to seal. In contrast, PFs that develop after pancreaticoduodenectomy represent a leakage of the pancreaticojejunal anastomosis, which cannot be sealed effectively by pancreatic duct stenting according to the results of Winter et al.25 Because stent dislocation after pancreatic duct stenting is common and stent occlusion may induce complications such as pancreatitis, we combined pancreatic stenting with sphincterotomy to ensure pancreatic duct decompression irrespective of the stent function. The combined success rate for pancreatic sphincterotomy and stenting was high (92%). The incidence of post-ERCP pancreatitis was estimated to be low because the risk of post-ERCP pancreatitis is decreased approximately threefold by pancreatic duct stenting.29 Indeed, early complications after stent placement were limited to 1 case of mild pancreatitis. In the 2 patients in whom stent placement failed, pancreatitis did not develop, although the risk of post-ERCP pancreatitis is increased by as much as 12.1% after pancreatic sphincterotomy without pancreatic stent placement.30 As in the study of Abe et al,31 post-ERCP pancreatitis occurred in a patient with an intraductal papillary mucinous tumor. Probably the mucin that is secreted by these tumors leads to early stent obstruction, with the risk of subsequent obstructive pancreatitis. The authors of this study concluded that preoperative stenting seems unsuitable for patients with this type of tumor. Even though the overall risk of postoperative pancreatitis seems low, preprocedure ERCP and stenting may be associated with periprocedural pancreatitis that could delay or preclude subsequent DP. We recommend stent placement for a period of 8 weeks to ensure that the resection site was healed and the patients had recovered from surgery. We are aware that stenting of the pancreatic duct can induce ductal changes that resemble the changes in chronic pancreatitis, but there seems to be no correlation of stent-induced changes with the duration of stenting.32 We did not assess by follow-up pancreatogram whether there were long-term sequelae of pancreatic stenting such as ductitis or papillary stenosis at the time of the stent removal. Another concern of long-term stenting of the pancreatic duct is stent occlusion. Ikenberry et al33 showed that the occlusion rate of pancreatic stents increased in a nearly linear fashion with the length of time that stents were left in the duct. In our patients, there were no clinically apparent cases of panwww.giejournal.org
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creatitis from stent occlusion before stent removal. The optimal duration of pancreatic stenting has yet to be defined. From an intent-to-treat standpoint, 5 patients were needed to be treated to prevent 1 PF. To prevent a PF that required a change in the clinical course (grades B and C), the number needed to treat was 8. The efficacy might be increased by risk stratification, restricting pancreatic duct stenting to patients with patient-related risk factors (age younger than 65 years,8 increased weight with a body mass index ⬎25,9,10 higher American Society of Anesthesiologists score,9 decreased albumin level,9 and impaired preoperative renal function11). In our study, all 5 patients in whom a PF developed had at least 1 patient-related risk factor. The main limitations of our study are the retrospective data capture within the control group and the singlecenter setting. Although the surgeon who performed the pancreatic resections was highly experienced at the beginning of the control period, it cannot be excluded that part of the better outcome in the endoscopic intervention group is because of an increase in experience, which might also be reflected in a shorter operating time in the stenting group. The advanced imaging techniques allow a higher detection rate and a more exact preoperative characterization, even of asymptomatic pancreatic lesions that are often located in the distal part of the pancreas. Therefore, the number of patients undergoing DP might increase in the future, making effective strategies to prevent postoperative complications even more important. In summary, although this retrospective study has potential selection biases, the findings suggest that preoperative pancreatic sphincterotomy and stenting are a feasible and safe procedure that prevented PF development after DP. Before recommending this intervention in clinical routine, a larger multicenter, randomized, prospective, controlled study is required to evaluate the benefit of this approach.
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Endoscopic pancreatic sphincterotomy and stenting 8. Yoshioka R, Saiura A, Koga R, et al. Risk factors for clinical pancreatic fistula after distal pancreatectomy: analysis of consecutive 100 patients. World J Surg 2010;34:121-5. 9. Goh BK, Tan YM, Chung YF, et al. Critical appraisal of 232 consecutive distal pancreatectomies with emphasis on risk factors, outcome, and management of the postoperative pancreatic fistula: a 21-year experience at a single institution. Arch Surg 2008;143:956-65. 10. Sledzianowski JF, Duffas JP, Muscari F, et al. Risk factors for mortality and intra-abdominal morbidity after distal pancreatectomy. Surgery 2005; 137:180-5. 11. Adam U, Makowiec F, Riediger H, et al. Pancreatic leakage after pancreas resection. An analysis of 345 operated patients [in German with English abstract]. Chirurg 2002;73:466-73. 12. Pannegeon V, Pessaux P, Sauvanet A, et al. Pancreatic fistula after distal pancreatectomy: predictive risk factors and value of conservative treatment. Arch Surg 2006;141:1071-6. 13. Ridolfini MP, Alfieri S, Gourgiotis S, et al. Risk factors associated with pancreatic fistula after distal pancreatectomy, which technique of pancreatic stump closure is more beneficial? World J Gastroenterol 2007;13: 5096-100. 14. Kleeff J, Diener MK, Z’graggen K, et al. Distal pancreatectomy: risk factors for surgical failure in 302 consecutive cases. Ann Surg 2007;245:573-82. 15. Suzuki Y, Fujino Y, Tanioka Y, et al. Randomized clinical trial of ultrasonic dissector or conventional division in distal pancreatectomy for nonfibrotic pancreas. Br J Surg 1999;86:608-11. 16. Takeuchi K, Tsuzuki Y, Ando T, et al. Distal pancreatectomy: is stapler closure beneficial? Aust NZ J Surg 2003;73:922-5. 17. Ferrone CR, Warshaw AL, Rattner DW, et al. Pancreatic fistula rates after 462 distal pancreatectomies: staplers do not decrease fistula rates. J Gastrointest Surg 2008;12:1691-7. 18. Suc B, Msika S, Fingerhut A, et al. Temporary fibrin glue occlusion of the main pancreatic duct in the prevention of intraabdominal complications after pancreatic resection. Ann Surg 2003;237:57-65. 19. Li-Ling J, Irving M. Somatostatin and octreotide in the prevention or postoperative pancreatic complications and the treatment of enterocutaneous pancreatic fistulas: a systematic review of randomized controlled trials. Br J Surg 2001;88:190-9. 20. Costamagna G, Mutignani M, Ingrosso M, et al. Endoscopic treatment of postsurgical external pancreatic fistulas. Endoscopy 2001;33:317-22.
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Rieder et al 21. Goasguen N, Bourrier A, Ponsot P, et al. Endoscopic management of pancreatic fistula after distal pancreatectomy and enucleation. Am J Surg 2009;197:715-20. 22. Abe N, Sugiyama M, Suzuki Y, et al. Preoperative endoscopic pancreatic stenting: a novel prophylactic measure against pancreatic fistula after distal pancreatectomy. J Hepatobiliary Pancreat Surg 2008;15:373-6. 23. Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery 2005;138:8-13. 24. Konishi T, Hiraishi M, Kubota K, et al. Segmental occlusion of the pancreatic duct with prolamine to prevent fistula formation after distal pancreatectomy. Ann Surg 1995;130:165-70. 25. Winter JM, Cameron JL, Campbell KA, et al. Does pancreatic duct stenting decrease the rate of pancreatic fistula following pancreaticoduodenectomy? Results of a prospective randomized trial. J Gastrointest Surg 2006;10:1280-90. 26. Hirota M, Kanemitsu K, Takamori H, et al. Local pancreatic resection with preoperative endoscopic transpapillary stenting. Am J Surg 2007;194: 308-10. 27. Fischer CP, Bass B, Fahy B, et al. Transampullary pancreatic duct stenting decreases pancreatic fistula rate following left pancreatectomy. Hepatogastroenterology 2008;55:244-8. 28. Renou C, Grandval P, Ville E, et al. Endoscopic treatment of the main pancreatic duct: correlations among morphology, manometry, and clinical follow-up. Int J Pancreatol 2000;27:143-9. 29. Singh P, Das A, Isenberg G, et al. Does prophylactic pancreatic stent placement reduce the risk of post-ERCP pancreatitis? A meta-analysis of controlled trials. Gastrointest Endosc 2004;60:544-50. 30. Hookey LC, RioTinto R, Delhaye M, et al. Risk factors for pancreatitis after pancreatic sphincterotomy: a review of 572 cases. Endoscopy 2006;38: 670-6. 31. Abe N, Sugiyama M, Suzuki Y, et al. Preoperative endoscopic pancreatic stenting for prophylaxis of pancreatic fistula development after distal pancreatectomy. Am J Surg 2006;191:198-200. 32. Smith MT, Sherman S, Ikenberry SO, et al. Alterations in pancreatic ductal morphology following polyethylene pancreatic stent therapy. Gastrointest Endosc 1996;44:268-75. 33. Ikenberry SO, Sherman S, Hawes RH, et al. The occlusion rate of pancreatic stents. Gastrointest Endosc 1994;40:611-3.
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