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