updates regarding role of ERCP drainage in Pancreatic cancer

1. ENDOSCOPIC BILIARY DRAINAGE IN
RESECTABLE PANCREATIC HEAD AND
PERIAMPULLARY MALIGNANCIES
Department of Surgical Oncology
Centre for Oncology
GRH,Royapettah
PROF.S.SUBBIAH et al.

2. PROF.S.SUBBIAH et al.
• ORIGINAL ARTICLE:
• Nationwide practice and outcomes of endoscopic biliary drainage in
resectable pancreatic head and periampullary cancer.
• JUNE 2020

3. PROF.S.SUBBIAH et al.
• JOURNAL : HPB
• IMPACT FACTOR: 3.647
• CITATION SCORE: 4.8
• AUTHORS: Anouk E.J. Latenstein1,*, Tara M. Mackay1,*, Nadine C.M. van
Huijgevoort2, Bert A. Bonsing3,
• Koop Bosscha4, Lieke Hol5, Marco J. Bruno6, Marielle M.E. van Coolsen7,
Sebastiaan Festen8,
• Erwin van Geenen9, Bas Groot Koerkamp10, Gerrit J.M. Hemmink11,
Ignace H.J.T. de Hingh12

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• COUNTRY: NETHERLANDS; MULTICENTER STUDY.
• RETROSPECTIVE

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• Patients with resectable pancreatic head and periampullary cancer may
require preoperative endoscopic biliary drainage (EBD) due to extrahepatic
bile duct obstruction.
• Early surgery is, however, preferred, as this is associated with fewer
perioperative complications compared to preoperative EBD.
• Indications for EBD include cholangitis, severe jaundice, long waiting
times for surgery, and the use of neoadjuvant therapy, which is a rapidly
emerging indication for longer-term EBD.

7. PROF.S.SUBBIAH et al.
• In the recently updated European Society of Gastrointestinal Endoscopy Clinical
Guideline, self-expanding metal stent (SEMS) placement is recommended in
case of preoperative EBD of malignant extrahepatic biliary obstruction.
• A potential downside of SEMS placement could be the increased risk of
postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis.
• Plastic stents are still frequently used, however, possibly because of lower upfront
costs.

8. PROF.S.SUBBIAH et al.
• The aim of this study was to assess the use of SEMS on a nationwide scale
in daily clinical practice in patients with pancreatic head and periampullary
cancer undergoing preoperative EBD and to determine the relation between
type of stent and EBD-related complications and postoperative outcomes.

9. PROF.S.SUBBIAH et al.
• This nationwide, retrospective cohort study included all patient with a pancreatic
ductal adenocarcinoma, distal cholangiocarcinoma, duodenal adenocarcinoma, and
ampulla ofVater adenocarcinoma who underwent pancreatoduodenectomy (PD)
between January 2017 and December 2018 after EBD in the Netherlands.
• In general, biliary drainage was considered indicated in patients with clinical
suspicion ofcholangitis (characterized by fever, abdominal pain and/or
jaundice), severe jaundice (bilirubin concentration 250 mmol/ or mild
jaundice (>25 mmol/L) before commencing neoadjuvant chemotherapy.

10. PROF.S.SUBBIAH et al.
Endoscopic ultrasound for obtaining pathological material is performed
prior to ERCP and stent placement. Type of stent depends on the expertise
and preference of the gastroenterologist. Prevention of post-ERCP pancreatitis
exists of rectal nonsteroidal anti-inflammatory drug administration and in
case of manipulation of the pancreatic duct, a 5 Fr plastic stent is placed in
the pancreatic duct. Patients with percutaneous biliary drainage were excluded.

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• Data collection
• Patient, tumor, and treatment characteristics were collected. Dates of the
final multidisciplinary team (MDT) meeting in pancreatic centers and of
drainage were available as well as type of stent and EBD-related
complications. No other data about stent replacement were available.
Postoperative outcomes were postoperative complications, in-hospital
mortality, length of hospital stay, and readmissions within 30 days after
discharge.

12. PROF.S.SUBBIAH et al.
• Data from patients with pancreatic head and periampullary cancer were
pooled in this study. Pancreatic centers were divided according to volume in
<40 or 40 PDs annually. Site of origin was categorized into pancreas, distal
bile duct, ampulla of Vater, duodenum, or other. Type of stent was
SEMS versus plastic stent. SEMS were categorized into fully covered
SEMS and uncovered SEMS. Neoadjuvant therapy was
chemo(radio)therapy, according to compliance with a randomised trial.

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• Preoperative pathological confirmation was obtained by duodenoscopy with
biopsy, ERCP with brush, or endoscopic ultrasound guided puncture of the
primary tumor. PD included pylorus-preserving PD, pylorus resecting PD,
and classical Whipple.
• EBD-related complications included pancreatitis, cholangitis, stent
occlusion, perforation of the bile duct or duodenum, and hemorrhage.
These complications were registered accordingly to judgement of the local
physicians.

14. PROF.S.SUBBIAH et al.
• All postoperative complications during hospital admission or up to 30 days
after resection were also registered. Major postoperative complications were
defined as a Clavien-Dindo score . Pancreatic surgery specific
complications (i.e.postoperative pancreatic fistula, delayed gastric emptying,
postpancreatectomy hemorrhage, and chyle leak) were defined by the
International Study Group on Pancreatic Surgery (ISGPS) and scored in
three groups of.

15. PROF.S.SUBBIAH et al.
• Bile leakage was scored accordingly as was defined by the International
Study Group of Liver Surgery. Grade B and C graded complications were
considered clinically relevant. Reintervention for a postoperative
complication was categorized as an endoscopic, radiological, or surgical
intervention.

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Clavien dindo classification of surgical
complications

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VARIOUS TYPES OF STENTS

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• PLASTIC STENTS:
• Smaller diameter
• Shorter duration/patency(< 3 months)
• Lesser cost
• More suitable for patients with less expected survival
• Easier to remove

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• METALLIC STENTS: Made of NITINOL. INCREASED PATENCY due to
increased diameter
• 3-4 times expensive than plastic stents
• Uncovered vs Partially covered vs Fully covered
• Covering is usually of SILICONE
• Mean duration of stay is around 1 year
• Covering prevents tumor ingrowth and improves patency, thereby facilitating
removal

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• The European guideline published in 2018 explicitly recommends the use of
SEMS in patients who undergo preoperative EBD. This recommendation is
mainly based on a meta-analysis that showed significantly lower rates of
endoscopic reinterventions and postoperative pancreatic fistula in patients
treated with SEMS compared to plastic stents (3.4% vs. 14.8% and 5.1%
vs.11.8%, respectively). This study shows, however, that over 50% of all
patients still received a plastic stent.

25. PROF.S.SUBBIAH et al.
• In the Netherlands both the recently completed PREOPANC-1 trial and the
ongoing PREOPANC-2 trial advise the use of (fully covered) SEMS prior
to start of neoadjuvant treatment. Naturally, the percentage of patients with
neoadjuvant therapy was higher in the SEMS group, but still a considerable
proportion of patients with neoadjuvant therapy received a plastic stent
(35%).

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• Several baseline characteristics differed between patients in the SEMS and
plastic stent groups. Differences in pancreatic texture and site of origin were
probably related to neoadjuvant therapy.
• The higher ASA score of patients with SEMS remains unexplained. It could
be that in patients with neoadjuvant therapy the ASA score increases during
treatment and that this score is registered after treatment shortly before
resection. More patients with a SEMS received neoadjuvant therapy and it
might be speculated that this (partly) causes the higher ASA score.

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• In this study, a similar rate of overall EBD-related complications was found
in the SEMS and plastic stent groups, but patients receiving plastic stents had
statistically significantly more EBD-related cholangitis compared to
patients receiving SEMS.
• This might also be the explanation for the longer time to surgery in patients
with a plastic stent. Surprisingly, the percentage of reinterventions was not
higher in the plastic stent group

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• It has been shown in previous studies that the frequency of EBD-
related pancreatitis was higher in patients with SEMS as compared to
plastic stents. SEMS and particularly fully covered SEMS could hamper
pancreatic duct out flow as compared to plastic stents which could increase
the risk of post-ERCP pancreatitis.
• In this nationwide study, it was not demonstrated that the post-ERCP
pancreatitis rate was higher inpatients with a SEMS, which was also
confirmed by several other studies.

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• Major postoperative complications were similar between the SEMS group and plastic
stent group. These results were comparable to the results of a meta-analysis.
• Literature is contradictive about the association between type of stent and postoperative
pancreatic fistula.
• In the current cohort, after adjustment for patient characteristics (i.e. age, sex, BMI, and
ASA score), hospital volume, neoadjuvant therapy, and other risk factors (i.e. BMI,
pancreatic texture, and pancreatic duct diameter; in accordance with the alternative fistula
risk score) in multivariable analysis, the odds of postoperative pancreatic fistula was
statistically significantly lower for patient who received a SEMS.

30. PROF.S.SUBBIAH et al.
• It is thought that the higher odds of postoperative pancreatic fistula is
related to pancreatic texture. The current binary classification of pancreatic
texture does not cover all variations in pancreatic texture. After expansion of
the SEMS, the pancreatic duct experiences more pressure and therefore
fibrosis of the pancreatic texture increases. More fibrosis is likely related to
less postoperative fistula.

31. PROF.S.SUBBIAH et al.
• RESULTS: In conclusion, this nationwide study found that EBD prior to
pancreatoduodenectomy still frequently involved plastic stents. SEMS
placement seemed to be associated with lower risks of cholangitis, less
postoperative pancreatic fistula, and a shorter postoperative hospital
stay but not with an increased risk of pancreatitis.
• A nationwide implementation strategy addressing both pancreatic centers
and regional referral networks might increase the use of SEMS, as
recommended by the European guideline.

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REFERNCES
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• 2. Dumonceau J-M, Tringali A, Papanikolaou I, Blero D, Mangiavillano B,
Schmidt A et al. (2018) Endoscopic biliary stenting: indications, choice of
stents, and results: European society of gastrointestinal endoscopy (ESGE)
clinical guideline – updated October 2017. Endoscopy,910–930.

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• 3.Gardner TB, Spangler CC, Byanova KL, Ripple GH, Rockacy MJ, Levenick JM et al.
(2016) Cost effectiveness and clinical efficacy of biliary stents in patients undergoing
neoadjuvant therapy for pancreatic adenocarcinoma in a randomized controlled trial. .
• 4. Adams MA, Anderson MA, Myles JD, Khalatbari S, Scheiman JM. (2012) Self-expanding
metal stents (SEMS) provide superior outcomes compared to plastic stents for pancreatic
cancer patients undergoing neoadjuvant therapy. J Gastrointest Oncol 3:309–313.
• 5. Seo DW, Sherman S, Dua KS, Slivka A, Roy A, Costamagna G et al(2019) Covered and
uncovered biliary metal stents provide similar relief of biliary obstruction during
neoadjuvant therapy in pancreatic cancer: a randomized trial. Gastrointest Endosc 90:602–
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