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Chapter 5: Preoperative biliary drainage for cancer of the head of the
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PhD thesis
Title
Challenging dogmas in pancreatic surgery: biliary drainage, outcome and
beyond
Author(s)
N.A. van der Gaag
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AMC-UvA
Year
2012

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5
Preoperative
Biliary Drainage
for Cancer of
the Head of
thePancreas

Niels A. van der Gaag

Erik A.J. Rauws
Casper H.J. van Eijck
Marco J. Bruno
Erwin van der Harst
Frank J.G.M. Kubben
Josephus J.G.M. Gerritsen
Jan Willem Greve
Michael F. Gerhards
Ignace H.J.T. de Hingh
Jean H. Klinkenbijl
Chung Y. Nio
Steve M.M. de Castro
Olivier R.C. Busch
Thomas M. van Gulik
Patrick M.M. Bossuyt
Dirk J. Gouma
New England Journal Of Medicine.
2010Jan;362(2):129-37

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Part I Preoperative Biliary Drainage for PancreaticCancer

ABSTRACT

78

Background
The benefits of preoperative biliary drainage, which was introduced to improve the
postoperative outcome in patients with obstructive jaundice caused by a tumor of the
pancreatic head, are unclear.
Methods
In this multicenter, randomized trial, we compared preoperative biliary drainage
with surgery alone for patients with cancer of the pancreatic head. Patients with
obstructive jaundice and a bilirubin level of 40 to 250 mol per liter (2.3 to 14.6 mg
per deciliter) were randomly assigned to undergo either preoperative biliary drainage
for 4 to 6 weeks, followed by surgery, or surgery alone within 1 week after diagnosis. Preoperative biliary drainage was attempted primarily with the placement of an
endoprosthesis by means of endoscopic retrograde cholangiopancreaticography. The
primary outcome was the rate of serious complications within 120 days after randomization.
Results
We enrolled 202 patients; 96 were assigned to undergo early surgery and 106 to
undergo preoperative biliary drainage; 6 patients were excluded from the analysis.
The rates of serious complications were 39% (37 patients) in the early-surgery group
and 74% (75 patients) in the biliary-drainage group (relative risk in the early surgery
group, 0.54; 95% confidence interval [CI], 0.41 to 0.71; P<0.001). Preoperative biliary
drainage was successful in 96 patients (94%) after one or more attempts, with complications in 47 patients (46%). Surgery-related complications occurred in 35 patients
(37%) in the early-surgery group and in 48 patients (47%) in the biliary drainage
group (relative risk, 0.79; 95% CI, 0.57 to 1.11; P=0.14). Mortality and the length of
hospital stay did not differ significantly between the two groups.
Conclusions
Routine preoperative biliary drainage in patients undergoing surgery for cancer of
the pancreatic head increases the rate of complications. (Current Controlled Trials
number, ISRCTN31939699.)

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79

BACKGROUND
Obstructive jaundice is the most common symptom in patients with periampullary cancer (located near the ampulla of Vater) or cancer of the pancreatic head. For
patients with a resectable tumor who have no radiologic evidence of metastasis, surgical resection is the only option for cure.1-3 Since surgery in patients with jaundice
is thought to increase the risk of postoperative complications, preoperative biliary
drainage was introduced to improve the postoperative outcome.4 In several experimental studies and retrospective case series, preoperative biliary drainage reduced
morbidity and mortality after surgery.4-7 However, two metaanalyses of randomized
trials and a systematic review of descriptive series showed that the overall complication rate in patients undergoing preoperative biliary drainage was higher than that in
patients who proceeded directly to surgery.8;9 This difference was partially explained
by complications associated with the preoperative biliary drainage procedure itself.
Nevertheless, preoperative biliary drainage has been incorporated into the surgical
treatment of cancer of the pancreatic head in many centers.10-12 To assess the rates of
serious complications and death and the length of hospital stay associated with preoperative biliary drainage, we conducted a multicenter, randomized trial comparing
the preoperative procedure, followed by surgery, with surgery alone.

METHODS
Study Design
We recruited patients 18 to 85 years of age who had a serum total bilirubin level
of 40 to 250 mol per liter (2.3 to 14.6 mg per deciliter) and no evidence on computed tomography (CT) of distant metastasis or local vascular involvement (which
was defined as tumor surrounding portal or mesenteric vessels for more than 180
degrees of their circumference or an irregular vessel margin). The interval between
CT and randomization was set to be less than 4 days. Endoscopic ultrasonography
was selectively performed if the CT findings were inconclusive.
Patients with a serious coexisting illness (Karnofsky performance score, <50 [on
a scale of 0 to 100, with higher scores indicating better performance]), another contraindication for major surgery, ongoing cholangitis, or previous preoperative biliary
drainage with stenting by means of endoscopic retrograde cholangiopancreaticography (ERCP) or percutaneous transhepatic cholangiography (PTC) were excluded.
Other exclusion criteria were the current receipt of neoadjuvant chemotherapy or
the presence of a serious gastric outlet obstruction (tumor-related duodenal stenosis,
which was defined by vomiting and an oral intake of <1 liter per day). All patients provided written informed consent. Patients were randomly assigned to undergo either
endoscopic preoperative biliary drainage for 4 to 6 weeks, followed by surgery, or
surgery alone within 1 week after diagnosis. Randomization, which was stratified
according to study center, was performed with a computer program at the coordi-

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nating trial center. The medical ethics committee at each study center approved the
protocol, which has been described previously.13

Part I Preoperative Biliary Drainage for PancreaticCancer

Study Oversight

80

The study coordinator collected data at each study site. The trial was sponsored by
the Netherlands Organization for Health Research and Development, which did not
have access to outcome data during the trial and did not participate in data analyses
or the preparation of the manuscript. The study coordinator, the clinical epidemiologist, and the lead academic author analyzed the data and vouch for the completeness
and accuracy of the analyses. No endoscopic equipment or stents were donated by the
manufacturer.

Endoscopic Preoperative Biliary Drainage

An attending gastroenterologist who was experienced in endoscopic preoperative biliary drainage performed the procedure using ERCP with plastic stent placement,
with or without antibiotic prophylaxis, according to local policy. If the procedure was
unsuccessful, the patient was referred to a tertiary center for a second attempt. PTC
with stent placement to achieve preoperative biliary drainage was considered a rescue
option in case of failed ERCP. Biliary drainage was defined as successful if the serum
bilirubin level decreased by 50% or more within 2 weeks after the procedure. A new
stent was placed if signs of inadequate bile drainage, with or without cholangitis,
developed. After 4 to 6 weeks of drainage, patients underwent surgery.

Surgery
Five academic and eight regional hospitals agreed to provide operating-room capacity
to ensure that early surgery could be performed as required by the protocol. Each of
the participating hospitals performed at least 10 resections of cancer of the pancreatic
head per year.
All patients received perioperative antibiotics. As prophylaxis only if indicated,
patients received vitamin K for coagulation disorders and octreotide or its analogues
for the treatment of a pancreas with a soft texture or a nondilated pancreatic duct.
The standard surgical procedure for resectable tumors was the pylorus-preserving
pancreatoduodenectomy, including removal of all lymph nodes on the right side of
the portal vein and mesenteric artery.14
If metastasis into the proximal duodenum or pylorus was suspected, a classic
Whipple procedure was performed, with resection of the distal stomach. If limited
metastasis into the portal or superior mesenteric vein was found, a wedge resection
of these vessels was included in the procedure.14;15 No specific modifications of surgical technique were expected for patients with jaundice, particularly with respect to
creating the hepaticojejunostomy. The extrahepatic bile duct becomes dilated after
distal obstruction, with concomitant induction of fibrosis in the duct wall, and usually remains dilated after preoperative biliary drainage because of decreased compliance of the duct. If resection was deferred because of metastasis or local spread,

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81

biopsy samples were obtained for histologic analysis. Palliative treatment generally
consisted of the creation of a hepaticojejunostomy with or without gastroenterostomy and celiac plexus neurolysis.14;16;17 If a hepaticojejunostomy was not feasible, an
expandable metal stent was inserted postoperatively by means of ERCP.

Evaluation of Outcomes
The primary outcome was the rate of serious complications up to 120 days after randomization, including any complication related to the drainage procedure or the surgical treatment that prompted an additional medical, endoscopic, or surgical intervention resulting in an extension of the hospital stay, readmission to the hospital, or
death. The definitions and management of complications have been used in previous studies evaluating the management of complications on the basis of generally
accepted criteria.18-25 (Definitions of all complications are listed in Table 1 in the Supplementary Appendix, available with the full text of this article at NEJM.org.) Secondary outcomes were mortality and the length of hospital stay. Symptoms or signs
of progressive or recurrent tumor within the study period were not considered as
treatment-related events. Outpatient visits were scheduled at 2, 6, and 12 weeks after
discharge. A standardized evaluation of symptoms and, if indicated, laboratory tests
and radiologic studies were performed at each visit. In addition, data regarding hospital admissions and all performed procedures were collected, with special attention
to any complication, including all additional endoscopic and surgical procedures.
When necessary, the patients physician was consulted for additional information.
To exclude bias in evaluating potential complications, an adjudication committee
reviewed all events in a blinded fashion and classified them as serious complications
or not serious, according to the definitions in the study protocol.13

Statistical Analysis
The principal analysis consisted of an intention-to-treat comparison of the proportion of patients with serious complications in the two treatment groups. The goal
was to test for noninferiority of early surgery, as compared with preoperative biliary drainage, with respect to the primary outcome, and superiority with respect to
secondary outcomes. Our previous meta-analysis was used to calculate the required
sample size.9
Assuming that there would be a complication rate of 38% in the early-surgery
group and 48% in the biliary-drainage group, we would consider early surgery to
be noninferior if the associated percentage of serious complications was less than
10 percentage points above the percentage of serious complications in the biliarydrainage group. We used a two-group large-sample normal approximation test of
proportions, with a one-sided significance level of 0.05, to test the null hypothesis
that early surgery would lead to an increase of at least 10 percentage points in the
rate of complications, as compared with preoperative biliary drainage, followed by
surgery. To attain a power of 80% to show noninferiority of early surgery, 94 patients
were needed in each group. We also performed a logistic-regression analysis of the

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82

complication rate with adjustment for potential prognostic factors of age, sex, bodymass index, tumor site (pancreatic vs. periampullary), and degree of jaundice. We
calculated two-sided 95% confidence intervals for all outcome measures.
After the enrollment of 50% of the patients, a safety committee (consisting of a
gastroenterologist, a surgeon, and a clinical epidemiologist) performed a planned,
blinded interim analysis of the primary outcome, for which the nominal significance
level was lowered to a more restrictive two-sided P-value of less than 0.01. The committee recommended the continuation of enrollment up to the calculated sample size.
202 Patients underwent randomization
6 Were excluded
4 Did not meet inclusion criteria
2 Withdrew consent

94 Were assigned to early surgery

5 Underwent PBD
3 Had logistic reasons
1 Had cholangitis
1 Had severe hyperglycaemia
2 Had surgical exploration deferred
1 Had choledocholithiasisat ERCP
1 Had pulmonary metastatic
disease

94 Were available for follow-up

102 Were assigned to PBD plus

surgery
6 Did not undergo PBD
2 Had choledocholithiasis
at ERCP
1 Had endoscopic removal
of polyp
1 Died of ERCP complication
2 Had technical failure
7 Had surgical exploration
deferred
2 Had choledocholithiasis
at ERCP
1 Had endoscopic removal
of polyp
1 Died of ERCP complications
2 Had unresectable tumor
after revision
1 Declined to undergo surgery

102 Were available for follow-up

Figure 1 Enrollment and Outcomes. ERCP denotes endoscopic retrograde

cholangiopancreaticography, and PBD preoperative biliary drainage.

RESULTS
Patients and Study Interventions
Between November 2003 and June 2008, a total of 202 patients underwent randomization (Fig. 1). After randomization, two patients withdrew consent, and four
patients were found to be ineligible because the serum total bilirubin level had not
been in accordance with the protocol before randomization. These six patients were
not included in the analyses. The demographic and clinical characteristics of the two
study groups were similar at baseline, with the exception of sex and body-mass index
(Table 1).

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83

Five patients who were assigned to the early-surgery group underwent preoperative biliary drainage for the following reasons: the surgical facility was not available
in time for early surgery (in the case of three patients), intercurrent cholangitis developed after earlier ERC without preoperative biliary drainage (in one patient), and
hyperglycemia (serum glucose level, 77 mmol per liter) developed (in one patient).
Table 1

Demographic and clinical characteristics of patients at randomization.*

Characteristic
Age yr
Male sex no. (%)
Body-mass index
Duration of symptoms wk
Median
Interquartile range
Weight loss kg
Median
Interquartile range
Bilirubin level mol/liter
Total
Direct
Cause of obstructive jaundice no. (%)
Adenocarcinoma
Neuroendocrine tumor
Cystic tumor
Chronic pancreatitis
Adenomatous bile-duct polyp
Choledocholithiasis

Early surgery
(N=94)

Preoperative
BiliaryDrainage
(N=102)

64.79.5
66 (70)
24.03.1

64.710.5
53 (52)
25.23.9

3
(2-6)

3
(2-6)

5
(3-8)

5
(3-10)

15158.7
10749.8

15459.5
11857.1

89 (95)
1 (1)
1 (1)
2 (2)
0
1 (1)

92 (90)
1 (1)
3 (3)
3 (3)
1 (1)
2 (2)

P-value
0.99
0.01
0.03
0.75

0.47

0.27
0.23
0.81

* Plus-minus values are means SD. To convert values for bilirubin to milligrams per deciliter, divide
by 17.1.
The body-mass index is the weight in kilograms divided by the square of the height in meters.
Weight loss was defined as the reduction in weight during the previous year.
The cause of obstructive jaundice was diagnosed on the basis of examination of a frozen section
obtained during surgery (if resection was not performed), a pathological specimen (if resection was
performed), or an endoscopic biopsy sample (if surgery was deferred).

Of the 102 patients in the biliary-drainage group 56 (55%) underwent a first attempt
at preoperative biliary drainage in a community hospital, and 46 (45%) underwent a
first attempt in an academic hospital. Adequate drainage was achieved in 77 patients
(75%) on the first attempt. The rates of successful initial stent placement in academic
centers and community hospitals did not differ significantly (83% and 69%, respectively; P=0.13). Symptoms that were associated with obstructive jaundice resolved
within 10 days after successful drainage. Reasons for initial failure of stent placement were an inability to cannulate the common bile duct in 12 patients with normal-

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84

appearing papilla, extensive tumor growth at the site of the papilla in 8 patients,
and failure to reach the papilla in 1 patient with a Billroth type II gastric resection.
After a second attempt, ERCP or PTC resulted in adequate drainage in 96 patients
(94%). Three patients did not undergo drainage because of misdiagnosed choledocholithiasis (in two patients) and endoscopic removal of an adenomatous polyp (in
one patient). There were technical failures in another three patients: failure of both
ERCP and PTC (in one patient), ERCP-associated bile-duct perforation for which an
emergency laparotomy with resection was performed (in one patient), and sphincterotomy-associated hemorrhage, which stopped the procedure (in one patient). The
patient with hemorrhage died 18 days later as a consequence of cholangiosepsis with
hemodynamic instability and preexisting cardiac failure.
The mean time to surgery was 1.2 weeks (95% confidence interval [CI], 0.9 to 1.4)
for the early-surgery group and 5.2 weeks (95% CI, 4.8 to 5.5) for the biliary-drainage
group. Surgical exploration was canceled in two patients in the early-surgery group
because of choledocholithiasis in one patient and pulmonary metastases of a previous breast carcinoma identified during the workup in the other. Seven patients in the
biliary-drainage group did not undergo surgery because of choledocholithiasis (in
two patients), earlier endoscopic polyp removal (in one patient), death after preoperative biliary drainage (in the abovementioned patient), unresectability after CT review
(in two patients), and the decision (on the part of one patient) not to undergo surgical treatment after successful stent placement. The percentages of patients undergoing resection did not differ significantly between the two groups: 63 patients in the
early-surgery group (67%) and 57 in the biliary-drainage group (56%) (P=0.11). The
surgical techniques were similar in the two groups. Table 2 in the Supplementary
Appendix lists additional procedural characteristics.

Complications
Table 2 lists the numbers of patients who had at least one complication related to
either preoperative biliary drainage or surgery. Complications that were associated
with preoperative biliary drainage occurred in 2 patients in the early-surgery group
(2%) and in 47 patients in the biliary-drainage group (46%). Of the 27 patients in
whom cholangitis developed (with or without stent occlusion), 3 patients had two
episodes. The mean interval from randomization to the first complication related
to preoperative biliary drainage in the biliary-drainage group was 13 days (95% CI,
10 to 16). Surgery-related complications occurred in 35 patients in the early-surgery
group (37%) and in 48 patients in the biliary-drainage group (47%), for a relative risk
of 0.79 (95% CI, 0.57 to 1.11) in the early-surgery group. There was no significant difference in surgical outcome between academic and community hospitals (P=0.21).
Figure 2 shows the cumulative proportion of patients in each group with one or
more complications. The rates of serious complications were 39% (37 patients) in
the early-surgery group and 74% (75 patients) in the biliary-drainage group; the relative risk of serious complications with early surgery was 0.54 (95% CI, 0.41 to 0.71)
(Table3).

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Table 2

85

Serious Complications within 120 days after Randomization.*

Complication

Early surgery
(N=94)

Preoperative Biliary
Drainage
(N=102)
no. (%)

Related to preoperative biliary drainage

Any
Pancreatitis
Cholangitis
Perforation
Hemorrhage after ERCP
Related to stent
Occlusion
Need for exchange
Related to surgery
Any
Pancreaticojejunostomy leakage
Grade A
Grade B
Grade C
Hemorrhage after pancreatectomy
Delayed gastric emptying
Biliary leakage
Gastrojejunostomy or duodenojejunostomy leakage
Intraabdominal abscess
Wound infection
Portal-vein thrombosis
Pneumonia
Cholangitis
Myocardial Infarction
Need for repeated laparotomy

2 (2)
0
2 (2)
0
0
1 (1)

47 (46)
7 (7)
27 (26)
2 (2)
2 (2)
15 (15)

2 (2)

31 (33)

35 (37)
11 (12)
1 (1)
4 (4)
6 (7)
4 (4)
9 (10)
3 (3)
2 (2)
3 (3)
7 (7)
1 (1)
5 (5)
3 (3)
0
13 (14)

48 (47)
8 (8)
0
4 (4)
4 (4)
2 (2)
18 (18)
1 (1)
4 (4)
2 (2)
13 (13)
0
9 (9)
3 (3)
4 (4)
12 (12)

* The numbers refer to patients who had one or more complications. ERCP denotes endoscopic
retrograde cholangiopancreaticography.
In two patients, cholecystitis occurred in connection with cholangitis, prompting antibiotic
treatment, without the need for cholecystectomy.
Hemorrhage was defined as bleeding that required the transfusion of at least 4 units of packed red
cells during a 24-hour period or bleeding that led to repeat laparotomy or another intervention.
Grade A refers to transient biochemical leakage that does not require treatment, grade B refers to
leakage that is managed with prolonged or percutaneous drainage, and grade C refers to leakage
requiring repeat laparotomy.
This category refers to complications of either preoperative biliary drainage or another surgical
procedure.

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86

Figure 2 Proportion of Patients with Complications.

The primary outcome the rate of serious complications within 120 days after
randomization occurred in 37 patients (39%) who underwent early surgery alone
and 75 patients (74%) who underwent preoperative biliary drainage (PBD) followed by
surgery (relative risk in the early-surgery group, 0.54; 95% confidence interval [CI],
0.41 to 0.71; P<0.001).

We rejected the null hypothesis of an increase in complications in the early-surgery

group (P<0.001 by a one-sided normal-approximation test). An additional test of
superiority showed that early surgery led to fewer complications than preoperative
biliary drainage (P<0.001). The difference was also significant in the logistic-regression analysis (P<0.001).
Patients in the biliary-drainage group, as compared with those in the early-surgery group, had significantly more readmissions for complications and stayed on
average 2 days longer in the hospital. There was no significant difference in mortality
between the groups. Among patients who underwent a palliative bypass procedure,
surgical complications developed in 18 of 33 patients (55%) in the biliary-drainage
group, as compared with 5 of 28 patients (18%) in the early-surgery group (P=0.003).

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Table 3

87

Major Outcomes.*

Variable
Overall protocol-specified
complications no. (%)
Preoperative biliary drainage
Surgery
Other complications
(not included in protocol) no. (%)
Death no. (%)
From protocol-specified complication
From any cause
Hospital readmission no. (%)
For protocol-specified complication
For any cause
Hospital stay days
For protocol-specified treatment
Median
Interquartile range
For any reason
Median
Interquartile range

Early surgery
(N=94)

Preoperative
Biliary Drainage
(N=102)

Relative Risk
(95%CI)

37 (39)

75 (74)

0.54 (0.410.71)

2 (2)
35 (37)
30 (32)

47 (46)
48 (47)
25 (25)

NA
0.79 (0.571.11)
1.30 (0.832.04)

4 (4)
12 (13)

9 (9)
15 (15)

0.48 (0.151.51)
0.85 (0.421.72)

11 (12)
18 (20)

34 (33)
40 (39)

0.35 (0.190.65)
0.49 (0.300.79)

13
(10-20)

15
(11-22)

14
10-21)

16
(11-22)

* The outcome numbers refer to patients who had one or more complications. NA denotes not
applicable.
The relative risks are for early surgery versus preoperative biliary drainage.
Other complications included urinary tract infection, chylous ascites, delirium, rectum prolapse,
clostridium infection, pulmonary embolism, cardiac arrhythmia, hypoglycemic coma, bladder
hemorrhage, catheter-related sepsis, and incisional hernia.
Hospital stays for protocol-specified treatment included admission for preoperative biliary drainage
(after randomization and performed on an inpatient basis), surgery, and necessary readmission for
any protocol-specified complication.

DISCUSSION
In this multicenter, randomized trial, we examined whether preoperative biliary
drainage should be performed routinely in patients with obstructive jaundice caused
by cancer of the pancreatic head before resection. We found that endoscopic preoperative biliary drainage with placement of a plastic stent did not have a beneficial effect
on the surgical outcome. Early surgery without preoperative biliary drainage did not
increase the risk of complications, as compared with preoperative biliary drainage,
followed by surgery.
The postoperative complication rate did not differ significantly between the two
groups, as has been reported previously.26-29 With respect to complications related
to endoscopic preoperative biliary drainage, the incidence of pancreatitis, perforation, or hemorrhage in our study was in accordance with the incidence reported by

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others.30-32 The rate of cholangitis associated with preoperative biliary drainage was
high and an important reason for readmission. This high incidence of cholangitis
was reported within the same range by all participating centers.
In contrast with earlier randomized studies, our study showed that preoperative
biliary drainage did not necessarily prolong the length of the hospital stay. The previously observed extended hospital stay can be attributed to the use of PTC drainage,
whereas endoscopic drainage, as used in our study, is often performed on an outpatient basis. The use of preoperative biliary drainage did not influence postoperative
mortality. Pancreatic surgery that is performed in high-volume centers is associated
with death rates that are well below 5%, an important argument for centralization of
such complex surgical procedures.26;33 In our study, the overall rate of death was 7%
(which included one patient who died after the biliary-drainage procedure) and did
not differ significantly between the two treatment strategies.
The optimal duration of biliary drainage before surgery has not been established.
Experimental and clinical studies have suggested that a period of at least 4 to 6 weeks
is needed for the restoration of normal major synthetic and clearance functions of
the liver, as well as mucosal intestinal barrier functions.4 A short period of drainage
may not lead to full recovery of the metabolic abnormalities associated with obstructive jaundice. In four randomized studies that did not show a benefit of preoperative
biliary drainage, the mean duration of drainage was 7 to 18 days.8 Our trial called
for 4 to 6 weeks of drainage. An even longer period would be unlikely to yield better
results, would increase the risk of stent occlusion and inflammation of the bile-duct
wall,9 and would result in a prolonged postponement of surgery that would be unjustifiable for a potentially resectable tumor.
Beneficial effects of preoperative biliary drainage were found in early, nonrandomized studies that involved a small number of patients and an imperfect methodologic design. In four of five randomized trials, preoperative biliary drainage by means
of PTC was the standard mode of drainage, whereas ERCP, a less invasive procedure,
is currently preferred.11 The consequences of percutaneous and endoscopic drainage
differ largely in terms of restoration of the enterohepatic cycle and bacterial colonization and inflammation of the biliary tract.4;7 The percutaneous route is reserved for
failed endoscopic attempts. In these studies, tumors causing proximal and distal bile
duct obstruction were included, but such tumors are now considered to be different
diseases and to require different forms of treatment.
With the advent of neoadjuvant chemotherapy used to downstage potentially
unresectable tumors in the hope of improving the outcome, the issue of preoperative biliary drainage is clinically relevant.34-36 In light of our poor results with plastic stents, preoperative biliary drainage during the period of neoadjuvant treatment
might be best achieved with metal stents, which have a higher patency rate than
plastic stents and do not affect the outcome of surgery.37-39

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with pancreatic cancer periampullary and
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(3) Phoa SS, Reeders JW, Rauws EA, De WL,
Gouma DJ, Lameris JS. Spiral computed
tomography for preoperative staging of
potentially resectable carcinoma of the pancreatic head. Br J Surg 1999; 86(6):789-794.
(4) van der Gaag NA, Kloek JJ, de Castro SM,
Busch OR, van Gulik TM, Gouma DJ. Preoperative Biliary Drainage in Patients with
Obstructive Jaundice: History and Current
Status. J Gastrointest Surg 2008.
(5) Klinkenbijl JH, Jeekel J, Schmitz PI,
Rombout PA, Nix GA, Bruining HA et al.
Carcinoma of the pancreas and periampullary region: palliation versus cure. Br J Surg
1993; 80(12):1575-1578.
(6) Trede M. The surgical treatment of pancreatic carcinoma. Surgery 1985; 97(1):28-35.
(7) Kimmings AN, Van Deventer SJ, Obertop
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