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Role of endoscopy in
pancreatic cancer
Abdul H Khan, M.D.
Associate Professor of Medicine
Division of Gastroenterology
Medical College of Wisconsin
10/5/2019
Disclosures
• I have no commercial interests to report
Pancreatic adenocarcinoma
clinical
• painless jaundice
• insidious abd/back pain
• anorexia/weight loss
• new onset diabetes
• elevated CA19-9
imaging
• pancreatic mass
• upstream ductal
dilation
• upstream panc
atrophy
• lymphadenopathy
• hepatic/other mets
Scenarios
• Pancreas mass
+ associated imaging features
+ typical clinical features
• Pancreas mass
– without associated imaging features
– without typical clinical features
• No pancreatic mass
+ associated imaging features
+ typical clinical features
Tissue diagnosis
If diagnosis in doubt
• neuroendocrine tumor
• cystic neoplasm
• focal pancreatitis
• ampullary carcinoma
• cholangiocarcinoma
• metastatic lesion
– RCC, breast
• lymphoma
• autoimmune pancreatitis
• ventral/dorsal pancreas
If surgery not immediate
• neoadjuvant chemoXRT
• palliative chemotherapy
• molecular profiling
Tissue diagnosisEUS
• preferred method of
obtaining tissue
diagnosis
• high sensitivity/specificity
• low complication rate
• low risk of tumor seeding
• staging
Tissue diagnosisEUS
• critical factors in accurate sampling
– endoscopic skill in identifying/sampling the lesion
– technician care/efficiency in processing the sample
– cytologist ability to interpret the slides
Tissue diagnosisEUS
courtesy
Vinod Shidham, MD
Tissue diagnosis- EUS
40x
Tissue diagnosisEUS
• retrospective study of 233pts (MD Anderson)
• CT- pancreatic mass suspicious of cancer
• 93% with final diagnosis of adenocarcinoma
• sensitivity 91%, specificity 100%, accuracy 92%
• most studies:
– sensitivity 75% to over 90%
– specificity 82-100%
– accuracy 85%Raut CP, et al. J Gastrointest Surg 2003
Boujaoude J, et al. Gastroenterol 2007
72M
• Painless jaundice, pruritis
• CA19-9 32
• CT- dilated bile duct, normal pancreas
• ERCP x 3- brushing neg, no amp mass
• EUS x 1- no mass
72M
• neoadjuvant
chemoXRT
– Gemzar
• R0 resection 8/1/12
– T1N0 (18 LN)
• adjuvant
chemotherapy
– FolFIRI x 8cycles
• asymptomatic
– CA19-9 10
CT- hop fullness or mass
EUS
• retrospective study of 693 pts
• EUS for suspicion of pancreatic cancer
• 155 normal pancreas on EUS
Klapmant JB, et al. Am J Gastro. 2005
EUS
• follow up info available on 135 (87%)
• mean follow up of ~2yrs (8-48mo)
• no pancreatic cancer detected during
follow up period
Klapmant JB, et al. Am J Gastro. 2005
EUSchronic calcific pancreatitis
Percutaneous FNA
• CT or transabdominal ultrasound
• disadvantages:
– lower sensitivity: randomized prospective study
• EUS 84%, percutaneous 62%
– higher risk of tumor seeding (skin/peritoneum)
• in retrospective study: 16.3%
• useful in sampling metastatic lesions
Micames C, et al. Gastrointest Endosc. 2003 Horwhat JD, et al. Gastrointest Endosc. 2006
Tissue diagnosisERCP
• “double duct sign”
suggestive of an
obstructive mass
• sampling of ductal
strictures
• placement of biliary
stent
Tissue diagnosisERCP
• study of ERCP-
sampling of strictures
suspicious for cancercytology
brush
De Billis, et al. Gastrointest Endosc. 2002
biopsy forceps
Tissue diagnosisERCP
Disadvantages
• low sensitivity
• only possible if ductal stricture present
• no staging information
• higher complication rates
• does not differentiate pancreatic
adenocarcinoma from cholangiocarcinoma
Staging
• primarily by CT scan
• EUS can add supplementary info
• EUS advantages:
– FNA of indeterminate lymph node, liver lesion
– small ascitic fluid sampling for cytology
– renal insufficiency prohibits CT
Staging
GDA
EUS
CT- panc body mass, no mets
EUS
Follow up
• palliative chemotherapy
• liver mets visible on CT after 10 mo
• passed away 2yrs after diagnosis
ComplicationsEUS
• retrospective study of EUS-FNA of pancreatic mass:
2/52 (3.8%)
– mild acute pancreatitis, mild hemorrhage
• prospective study of 22g vs 25g needle for pancreatic
cancer at a tertiary center: 131 patients
– no complications
• retrospective study- pancreatic EUS at a Univ in Italy:
3259 cases with 1034 EUS-FNA
– 0.29% major complications:
• 2 severe pancreatitis
• 1 duodenal perforation/death
– 1% mild self limited bleeding
Siddiqui, et al. Gastrointest Endosc. 2009
Ardengh, et al. J Panc. 2009
Obstructive jaundice
• Surgery upfront
• Neoadjuvant therapy
• Palliative therapy
Obstructive jaundice
• Surgery upfront
• Neoadjuvant therapy
• Palliative therapy
Obstructive jaundice
• randomized multicenter prospective trial
• resectable panc ca w/obstructive jaundice
• immediate surgery vs preoperative biliary
drainage followed by surgery after 4-6wks
• no neoadjuvant therapy
• primary outcome: rate of serious
complications within 120d of
randomization
van der Gaag, et al. NEJM. 2010
• 202 patients
• 94 early surgery
• 102 biliary decompression before surgery
– 75% success on 1st ERCP
• 83% tertiary center, 69% community (p=.13)
– 94% ultimately successful (reduced bili by 50%)
Obstructive jaundice
van der Gaag, et al. NEJM. 2010
Preoperative complications
Early surgery group
• Cholangitis 2%
Biliary drainage group
• Total 46%
• Cholangitis
• Pancreatitis
• Hemorrhage
• Duodenal perforation
• Death (1)
van der Gaag, et al. NEJM. 2010
• plastic stents used, no metal stents
• pts with bilirubin > 15 excluded
• waited 4-6wks before surgery
Obstructive jaundice
van der Gaag, et al. NEJM. 2010
Obstructive jaundice
• Surgery upfront
• Neoadjuvant therapy
• Palliative therapy
Obstructive jaundice
• options: ERCP, PTC
• ERCP allows natural drainage
• PTC more painful; requires external bag
Obstructive jaundiceERCP
• sphincterotomy followed by stent
• plastic 10Fr or metal 10mm diameter
• malignant strictures lead to faster stent
occlusion than benign strictures
plastic
metal
Obstructive jaundiceERCP
• retrospective study, N 272
• obstructive jaundice, pancreatic cancer
• biliary drainage
– plastic vs metal stents
• neoadjuvant treatment
• Whipple surgery
Mullen, et al. J Gastrointest Surg 2005
Average cost/pt ($) $2700 $3450 ($750)
Mullen, et al. J Gastrointest Surg 2005
Obstructive jaundiceERCP
• prospective study, MCW
• pancreatic cancer, neoadj therapy
• 55pts with metal stent placement
– 23 resectable, 32 borderline resectable
• neoadj phase 70-260 days
• median time to surgery 104 days
Aadam AA, et al. Gastrointest Endosc 2012
Obstructive jaundiceERCP
• metal stent normalized LFTs in all pts
• 52 pts started neoadjuvant therapy
– 21 (40%) no surgery
• 17 disease progression
• 4 co-morbidity
– 31 (60%) surgery with intention of Whipple
• 27 Whipple (50%)
• 4 metastatic disease
Aadam AA, et al. Gastrointest Endosc 2012
Obstructive jaundiceERCP
Aadam AA, et al. Gastrointest Endosc 2012
Obstructive jaundiceERCP
• 8 stent related complications at 260 days
– occlusion 4 (uncov 3, cov 1)
– occlusion/cholangitis 3 (uncov)
– cholecystitis 1 (uncov)
– includes one stent migration
• mild post ERCP pancreatitis 3
• no surgical difficulty due to stent
Aadam AA, et al. Gastrointest Endosc 2012
Common errors
• Abdominal pain with elevated LFTs
– ultrasound shows cholelithiasis
– surgeon performs cholecystectomy
Common errors
• Abdominal pain with elevated LFTs
– ultrasound shows cholelithiasis
– surgeon performs cholecystectomy
• Painless jaundice
– ultrasound shows biliary dilation
– gastroenterologist performs ERCP
“Gallstones”
• Abdominal pain and either:
– elevated LFTs (w/o jaundice)
– weight loss
• Gallstones only cause abdominal pain
• Other possibilities
– choledocholithiasis/Mrizzi’s syndrome
– fatty liver
– pancreatic cancer (gallstones from stasis)
“Gallstones”
• Abdominal pain and either:
– elevated LFTs (w/o jaundice)
– weight loss
• Gallstones only cause abdominal pain
• Other possibilities
– choledocholithiasis/Mrizzi’s syndrome
– fatty liver
– pancreatic cancer (gallstones from stasis)
• CT with contrast
Painless jaundice
• Ultrasound- dilated bile duct
• ERCP performed
– stricture found; sampled for cytology
– plastic stent placed
• Cytology negative for malignancy
• Jaundice improves, patient thankful
Painless jaundice
• Ultrasound- dilated bile duct
• ERCP performed
– stricture found; sampled for cytology
– plastic stent placed
• Cytology negative for malignancy
• Jaundice improves, patient thankful
• Eventually, CT shows pancreatic mass
Painless jaundice
• Jaundice is NOT a medical emergency
• Intervention affects quality of imaging for
staging
• EUS-FNA far superior to ERCP for tissue
diagnosis
Painless jaundice
• Jaundice is NOT a medical emergency
• Intervention affects quality of imaging for
staging
• EUS-FNA far superior to ERCP for tissue
diagnosis
• Do not rush to ERCP
Painless jaundice approach
• LFT, tumor markers
(CEA, CA19-9)
• high quality CT
– prior to endoscopy**
• EUS-FNA for tissue
diagnosis/staging
– real time preliminary
cytology reading
• ERCP/stent in same
session
• neoadjuvant
chemoradiation or
palliation
Failed ERCP
• Re-attempt ERCP
• EUS-guided rendezvous biliary access
• Percutaneous rendezvous with ERCP
• Percutaneous drain
• Surgery
Failed ERCP
• Re-attempt ERCP
• EUS-guided rendezvous biliary access
• Percutaneous rendezvous with ERCP
• Percutaneous drain
• Surgery
Re-attempt ERCP
• Cohort study at tertiary care in Australia
• 51pts referred with failed ERCP
– bile duct stones 45%
– malignant stricture 18%
– benign stricture/bile leak 11%
• Successful ERCP 100%
– required needle knife for access 27%
– post ERCP pancreatitis 3.9%
Swan MP, et al. World J Gastroenterol. 2011
Re-attempt ERCP
• Tertiary care center
– higher volume of ERCP
– more experience with complex cases
– riskier techniques (needle knife)
– available expertise in case of complication
Failed ERCP
• Re-attempt ERCP
• EUS-guided rendezvous biliary access
• Percutaneous rendezvous with ERCP
• Percutaneous drain
• Surgery
EUS-biliary access
• EUS used to puncture biliary tree and
pass wire down through ampulla to
facilitate ERCP
• Requires very dilated biliary tree
1
2
EUS-biliary access via CBD
• Obstructive jaundice, 3.5cm hop mass
• EUS-FNA positive for malignancy
• Failed ERCP due to ampullary edema
EUS-biliary access
via L intrahepatic ducts
Failed ERCP
• Re-attempt ERCP
• EUS-guided rendezvous biliary access
• Percutaneous rendezvous with ERCP
• Percutaneous drain
• Surgery
Percutaneous rendezvous with
ERCP• Combined IR/GI procedure
• Percutaneous biliary access with passage
of wire only to duodenum
• Wire grasped at ampulla via endoscopy to
allow ERCP
• Sphincterotomy/metal stent placed
Percutaneous rendezvous with
ERCP• Combined IR/GI procedure
• Percutaneous biliary access with passage
of wire only to duodenum
• Wire grasped at ampulla via endoscopy to
allow ERCP
• Sphincterotomy/metal stent placed
• Percutaneous drain not placed
Failed ERCP
• Re-attempt ERCP
• EUS-guided rendezvous biliary access
• Percutaneous rendezvous with ERCP
• Percutaneous drain
• Surgery
Percutaneous drain
• Not favored
• routine drain exchanges interrupt
neoadjuvant therapy
• risk of infection
• patient dislike percutaneous bag
• patient discomfort
• risk of tumor seeding
Percutaneous drain
• Used in 3 settings
1.Gastric outlet obstruction prevents ERCP
2.Gastric bypass anatomy prevents ERCP
3.Hilar stricture (cholangiocarcinoma)
– more durable drainage than ERCP
– drain in non affected liver segment useful
during surgical resection
EUS/ERCP in gastric bypass
• EUS-guided access to defunctionalized
stomach using Axios stent
• Tract matures
• Axios removed, fistula balloon dilated to
allow passage of EUS/ERCP scope to
duodenum for FNA and stent
Gastric outlet obstruction
Gastric outlet obstruction
• 51M locally advanced cancer in the
pancreatic body
• rapid growth despite chemotherapy
• obstructive jaundice
• ERCP- metal biliary stent placement
• n/v and distention one week later
Gastric outlet obstructionsurgery vs endoscopic stent
• RCT- GOO due to unresectable pancreatic cancer
• Randomized to
– endoscopic metal stent 21
– surgical gastrojejunostomy 18
• no difference in major complications, mortality
• Stent group
– shorter hospital stay, quicker resolution of GOO
• Surgical group
– better duration of relief
– favored if survival > 2mo
Jeurnink SM, et al. Gastrointest Endosc 2010
Endoscopic gastroenterostomy
• non operable pancreatic cancer
• gastric outlet obstruction
• failed/occluded metal duodenal stent
Endoscopic gastroenterostomy
• direct connection:
– gastric body to distal
duodenum
• lumen opposing metal
stent (Axios)
Itoi T, et al. Dig Endosc 2017
Endoscopic gastroenterostomy
Rimbas M, et al. Endoscopic Ultrasound. 2017
Endoscopic gastroenterostomy
Itoi T, et al. Dig Endosc 2017
Endoscopic gastroenterostomy
Itoi T, et al. Dig Endosc 2017
Endoscopic gastroenterostomy
Itoi T, et al. Dig Endosc 2017
EUS vs surgical GJJ
• multicenter- 3 US, 1 Japan
• retrospective cohort study
• malignant GOO
• EUS 30, surgery 63
Khasab MA, et al. Endosc Int Open 2017
Endoscopic gastroenterostomy
Rimbas M, et al. Endoscopic Ultrasound. 2017
22
(73%)
2
(7%)
6
(20%)
Khasab MA, et al. Endosc Int Open 2017
EUS vs surgical GJJ
Khasab MA, et al. Endosc Int Open 2017
Complications
EUS 5 (16%)
• Peritoneal placement 3
• Abdominal pain 2
• Severe 3 (hosp > 10d)
• Fatal 0
Surgical GJJ 16 (25%)
• Infection 8
• Anastomotic leak 4
• Persistent ileus 1
• Delirium 2
• Pulmonary embolism 1
• Severe- None
• Fatal 0
Khasab MA, et al. Endosc Int Open 2017