Role of endoscopy in pancreatic cancer · 2019-11-11 · Pancreatic adenocarcinoma clinical •...

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


• study of ERCP-

sampling of strictures

suspicious for cancercytology

brush

De Billis, et al. Gastrointest Endosc. 2002

biopsy forceps


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

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


• 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%)



Preoperative complications

Early surgery group

• Cholangitis 2%

Biliary drainage group

• Total 46%

• Cholangitis

• Pancreatitis

• Hemorrhage

• Duodenal perforation

• Death (1)


• plastic stents used, no metal stents

• pts with bilirubin > 15 excluded

• waited 4-6wks before surgery




• Surgery upfront

• Neoadjuvant therapy

• Palliative therapy


• 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


• 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


• 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


• 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



• 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


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

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




• Surgery

EUS-biliary access

• EUS used to puncture biliary tree and

pass wire down through ampulla to

facilitate ERCP

• Requires very dilated biliary tree

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




• 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




• 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


• direct connection:

– gastric body to distal

duodenum

• lumen opposing metal

stent (Axios)

Itoi T, et al. Dig Endosc 2017


Rimbas M, et al. Endoscopic Ultrasound. 2017


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


Rimbas M, et al. Endoscopic Ultrasound. 2017

22

(73%)

2

(7%)

6

(20%)


EUS vs surgical GJJ


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


Role of endoscopy in pancreatic cancer · 2019-11-11 · Pancreatic adenocarcinoma clinical •...

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