EUS in the Management of Pancreaticobiliary CancersPancreaticobiliary Cancers

Frank Gress, MDProfessor of Medicine and ChiefProfessor of Medicine and Chief

Division of Gastroenterology and HepatologyState University of New YorkState University of New YorkDownstate Medical Center

Brooklyn, NY

• "EUS for the Diagnosis Staging FNA andEUS for the Diagnosis, Staging FNA and Celiac Neurolysis of Pancreatic Cancer”

Pancreatic AdenocarcinomaPancreatic Adenocarcinoma

• The fourth leading cause of cancer-related gdeath in the U.S.

• At diagnosis only ~15% of patients are did t f ticandidates for curative surgery

• Five-year survival following a Whipple procedure was only 25% for nodeprocedure was only 25% for node-negative tumors and 10% for node-positive tumorsp

Ahmad et al. Long term survival after pancreatic resection for pancreatic adenocarcinoma The American Journal of Gastroenterolpancreatic adenocarcinoma. The American Journal of Gastroenterol 2001;96(9):2609-15

Pancreatic CancerPancreatic Cancer

• Late presentation, aggressive nature and lack of p , ggeffective therapies all contribute to the poor prognosis

• Early detection is crucial to improve the overall prognosisprognosis

• Accurate Staging is vital for selecting the subset• Accurate Staging is vital for selecting the subset of patients who have potentially resectable tumors

Common Indications for EUSCommon Indications for EUS

GI Tumor StagingGI Tumor Staging

Esophageal Cancer Gastric CancerRectal Cancer Ampullary CancerAmpullary Cancer Pancreatic Cancer

Cancer StagingCancer Staging

EUS Staging Accuracy Compared to PathEUS Staging Accuracy Compared to PathIndication n T stage N stageE h l CA 739 85% 79%Esophageal CA 739 85% 79%Gastric CA 1163 78% 73%

C % %Pancreatic CA 155 90% 78%Ampullary CA 94 86% 72%Rectal CA 19 84% 84%

Clinical Applications for EUSClinical Applications for EUS

Pancreatic and Biliary DiseasePancreatic and Biliary DiseaseTumor StagingLocalization of Endocrine TumorsDetecting CholedocholithiasisgDetecting Chronic Pancreatitis

EUS Indications for StagingEUS Indications for StagingEUS Indications for StagingEUS Indications for Staging

•• Pancreatic MassesPancreatic Masses–– AdenocarcinomaAdenocarcinoma–– Other malignancies/metastasesOther malignancies/metastases

•• Bile duct cancer (cholangiocarcinoma)Bile duct cancer (cholangiocarcinoma)

Clinical Applications for EUSClinical Applications for EUS

Current IndicationsCurrent IndicationsPancreatic and Biliary Malignancies1) Tumor staging primarily based on ability

to assess for vascular invasion2) Localization of Endocrine Tumors3) Ability to sample lesions for diagnosis

with >85% accuracy

Pancreatic Tumor StagingPancreatic Tumor Staging

EUS Stations for Staging P i TPancreatic Tumors

Transducer Major Structures jLocation identified with EUS

Gastric Body Confluence, Body/Tail of Pancreas PD Celiacof Pancreas, PD, Celiac Axis, Splenic vessels, SMA

Gastric Antrum Gallbladder,Liver,PancreasDuodenum

Bulb Head of Pancreas CBD PDBulb Head of Pancreas, CBD, PD 2nd Portion Head of Pancreas, SMA/SMV,

Aorta, PD, Ampulla, Liver

EUS Staging of Pancreatic CancerEUS Staging of Pancreatic Cancer

TNM ClassificationTNM Classification

T Staging is based on tumor size depth ofT Staging is based on tumor size, depth of invasion and infiltration into major vessels

N Staging assesses for nodal involvement

M Staging denotes the absence/presence distant metastasis (EUS can detect hepatic metastasis)

T2 Pancreatic MassT2 Pancreatic Mass

T3 Pancreatic AdenocarcinomaT3 Pancreatic Adenocarcinoma

T3 Pancreatic TumorT3 Pancreatic Tumor

Pancreatic MassPancreatic Mass

EUS Detection Rates of Pancreatic Tumors

Sensitivity (%) Specificity (%) PPV(%) NPV(%) AccuracySensitivity (%) Specificity (%) PPV(%) NPV(%) Accuracy (%)

Rosch, 1991 99 100 100 97 76

Snady 1992 85 80 89 73Snady, 1992 85 80 89 73 83

Yasuda, 1993 - - - - 100

Muller 1994 94 100 - -Muller, 1994 94 10096

Gress, 1997 93 100 - - -

Baron, 1997 95 88 95 88Baron, 1997 95 88 95 88-

Legmann, 1998 100 93 - - -

Akahoshi, 1998 89 97 94 93Akahoshi, 1998 89 97 94 9394

Totals 95 94 95 88 90

Pancreatic Cancer Staging by EUSPancreatic Cancer Staging by EUS

Pooled DataPooled Data

• T staging accuracy ranges from 78 to 94% • T staging accuracy is higher in patientsT staging accuracy is higher in patients

with advanced lesions (T3 and T4)• Vascular invasion accuracy was 82 to 93%• Vascular invasion accuracy was 82 to 93%• N staging accuracy ranges from 64 to 82%

Diagnosis by EUSDiagnosis by EUS

• EUS provides improved imaging of small tumors p p g gnot seen with other imaging modalities

• The detection of pancreatic tumors < 3 cm in diameter was higher for EUS:diameter was higher for EUS:

EUS (100%) ( )TUS (57%) CT (68%)

Rosch, et al. Endoscopic ultrasound in small pancreatic tumors. Z Gastroenterol 1991;29:110-5.

Diagnosis by EUSDiagnosis by EUS

• The detection of pancreatic tumors < 2cm in pdiameter was higher for EUS:

EUS (100%)EUS (100%) ERCP (57%)TUS (29%)TUS (29%) CT (29%) Angiography (14%)

Yasuda K, et al. The diagnosis of pancreatic cancer by endoscopic ultrasonography. Gastrointest Endosc 1998;34:1.

EUS StagingEUS Staging

Lower T and N staging accuracy has also beenLower T and N staging accuracy has also been described:

• 89 patients with pancreatic cancer had EUS p pstaging compared to surgery

• Overall accuracy for T staging was 69% and for y g gN staging was 54%

• Only 46% of tumors designated by EUS as resectable actually were at laparotomy

Ahmad et al Gastrointest Endo 2000;52:46Ahmad,et al Gastrointest Endo 2000;52:46

Pancreatic CancerPancreatic CancerPancreatic CancerPancreatic Cancer

•• Best modality for small lesionsBest modality for small lesions•• Diagnostic imaging and fine needle Diagnostic imaging and fine needle

aspiration during single procedureaspiration during single procedurep g g pp g g p•• Evaluate for chronic pancreatitis if Evaluate for chronic pancreatitis if

not tumor foundnot tumor foundnot tumor foundnot tumor found•• All pancreatic cancer has a dismal All pancreatic cancer has a dismal

prognosisprognosisprognosisprognosis

Liver MetastasisLiver Metastasis

LiverLiver

• EUS provides excellent imaging of theEUS provides excellent imaging of the liver particularly the left lobe of the liver and some portions of the right lobeand some portions of the right lobe

• The left lobe is best seen from the gastric body and fundusbody and fundus

• The right lobe is best imaged from the t d d dantrum and duodenum

Clinical Utility of EUS FNA for Di i Li l iDiagnosing Liver lesions

l Sensitivity of EUS-FNA for the diagnosis ofl Sensitivity of EUS FNA for the diagnosis of malignancy ranged from 82 to 94%

l When compared with benign lesions, EUS p g ,features predictive of malignant hepatic masses were the presence of regular outer margins (60% vs 27%; p = 0.02) and the detection of two or more lesions (38% vs 9%; p = 0 03)p = 0.03).

[DeWitt J et al. Am J Gastroenterol. 2003 Sep;98(9):1976-81]81]

EUS IndicationsEUS IndicationsC S iC S iCancer StagingCancer Staging

•• AmpullaryAmpullaryM t t l i l t iM t t l i l t iMost accurate locoregional stagingMost accurate locoregional staging

•• RectalRectalMost accurate locoregional stagingMost accurate locoregional staging

•• Other e.g. duodenal tumors,Other e.g. duodenal tumors,Other e.g. duodenal tumors, Other e.g. duodenal tumors, adenomasadenomas

T1 Ampullary TumorT1 Ampullary TumorT1 Ampullary TumorT1 Ampullary Tumor

Limitations of EUSLimitations of EUS

• Factors influencing EUS staging accuracy:Factors influencing EUS staging accuracy:– Experience level of endosonographer

Imaging artifacts/Normal variants/Chronic– Imaging artifacts/Normal variants/Chronic Pancreatitis

– Distinguishing vascular compression from– Distinguishing vascular compression from tumor infiltration can be difficult in larger tumors

– Accuracy for detecting invasion into the SMA and SMV is lower than that for PV or SV

EUS versus Helical CTEUS versus Helical CT

Contrast enhanced helical CT has been compared to EUS for detecting pancreatic tumors, predicting resectability and determining vascular invasionvascular invasion

Leggmann, et al; 1998Leggmann, et al; 1998 Midwinter, et al; 1999 Mertz, et al; 2000Tierney, et al; 2002

EUS versus Helical CTEUS versus Helical CT

Pooled DataAccuracy

4 Studies n=164 EUS CTDetecting pancreatic tumors 97% 73%

Predicting resectability 91% 83%

Determining vascular invasion 91% 64%Determining vascular invasion 91% 64%

Hunt GC, et al. Gastrointest Endosc 2002;55:232.

EUS versus Helical CTEUS versus Helical CT

Several features of the individual studies may account for the disparity in the conclusions:p y- Differences in Gold Standard- Differences in Helical CT TechniqueDifferences in Helical CT Technique - Number of patients with advanced disease

EUS versus Multidetector CTEUS versus Multidetector CT

• Prospective study comparing EUS and p y p gMultidetector CT for detecting and staging pancreatic cancer

120 patients with known pancreatic cancer

EUS was:98% sensitive for tumor detection (86% for CT) 67% for tumor staging accuracy (41% for CT)67% for tumor staging accuracy (41% for CT) 44% for nodal staging accuracy (47% for CT)

DeWitt J, et al. Comparison of EUS and Multidetector CT for detecting and staging pancreatic cancer. Annals of Internal Med 2004;141:753-63

EUS versus Helical CTEUS versus Helical CT

ConclusionsConclusions

EUS d H li l CT l t f• EUS and Helical CT are complementary for staging pancreatic cancer.

• EUS is a more accurate modality for T staging and predicting vascular invasion and CT isand predicting vascular invasion and CT is better for detecting distant metastasis.

EUS and Cancer DiagnosisEUS and Cancer DiagnosisEUS and Cancer DiagnosisEUS and Cancer Diagnosis

•• Controversial whether preControversial whether pre--operativeoperativeControversial whether preControversial whether pre--operative operative diagnosis is necessarydiagnosis is necessary

•• Direct to resection when clinicalDirect to resection when clinical•• Direct to resection when clinical Direct to resection when clinical suspicion is highsuspicion is high

vs.vs.•• PrePre--operative tissue diagnosisoperative tissue diagnosis

Role of EUS inR t C ft Whi lRecurrent Cancer after Whipple

EUS-FNA of Pancreatic LesionsEUS FNA of Pancreatic Lesions

Not all pancreatic masses are cancerNot all pancreatic masses are cancerDifferential Diagnosis

• Adenocarcinoma• Neuroendocrine tumorNeuroendocrine tumor• Lymphoma

Chronic pancreatitis• Chronic pancreatitis

Normal PancreasNormal PancreasNormal PancreasNormal Pancreas

EGEG--3630UR3630UR

Normal PancreasNormal PancreasNormal PancreasNormal Pancreas

EGEG--3630UR3630URGFGF--UM130UM130

Pancreatic CancerPancreatic CancerPancreatic CancerPancreatic Cancer

Islet Cell TumorIslet Cell TumorIslet Cell TumorIslet Cell Tumor

Chronic PancreatitisChronic PancreatitisChronic PancreatitisChronic Pancreatitis

EGEG--3630UR3630UR

EUS-guided Fine Needle AspirationEUS guided Fine Needle Aspiration

• Percutaneous or CT-guided biopsy has been thePercutaneous or CT guided biopsy has been the traditional approach for establishing the diagnosis of pancreatic cancer

• EUS FNA was introduced ~10 years agoy g

• The main advantage of EUS guided FNA biopsy e a ad a tage o US gu ded b opsyis its ability to obtain tissue sampling of any suspicious mass found during EUS evaluation.

Fi N dl A i tiFi N dl A i tiFine Needle AspirationFine Needle Aspiration

EUS FNA Needles

Diagnostic Characteristics of EUS FNA gfor Pancreatic Mass Lesions

n Sensitivity (%) Specificity (%) Accuracy (%)

Giovannini [Endoscopy 1995;27(2)] 43 75 100 79

Cahn [AJS 1996;172(5)] 50 88 100 87

Bhutani [Endoscopy;1997;29(9)] 47 64 100 72Bhutani [Endoscopy;1997;29(9)] 47 64 100 72

Chang [GIE;1997;45(5)] 44 92 100 95

Erickson [AFP 1997;55(6)] 28 -- -- 96

Faigel [JClinOnc1997;15(4)] 45 72 100 75

Gress [GIE1997;45(3)] 12180 100 85

Wiersema [Gastro 1997;112(4)] 124 87 100 88

Binmoeller [GIE1998;47(2)] 5876 100 92

560 81% 100% 86%

RESULTS OF EUS-GUIDED FNA BIOPSY IN PATIENTS WITH OR WITHOUT PANCREATIC

CANCEREUS- Guided Patients with Patients without LikelihoodFNA BX P ti CA P ti CA R ti (95% (CI)FNA BX Pancreatic CA Pancreatic CA Ratio (95% (CI)

Positive results 57/61 (93.%) 0/41 (0) All values ≥9.7+

Negative results 3/61 (4.9%) 34/41 (83%) 0.05 (0.02-0.15)

Inconclusive or 1/61 (1.6%) 7/41 (17.%) 0.096 (0.012-0.75)

nondiagnosticnondiagnostic

(G F l A I M d 2001 134(6) 4 9 464)(Gress F, et.al. Ann Int Med 2001; 134(6):459-464)

EUS-Guided FNAEUS Guided FNA

Reported Complications:Reported Complications:

• Infection (cysts >>solid mass)Infection (cysts >>solid mass)• Pancreatitis (<1- 2%)• Bleeding• Bleeding

EUS-Guided FNAEUS Guided FNA

Reported Complications:Reported Complications:InfectionBleeding

Pancreatitis (2-4%)( )100 patients having EUS FNA of pancreas

[Gress et al GIE 2003][Gress, et al GIE 2003]- 2/100 developed clinical pancreatitis

Transient Elevations in enzymes occur- Transient Elevations in enzymes occur

Pancreatic MassPancreatic Mass

Neuroendocrine TumorNeuroendocrine Tumor

Advantages over CT-guided BiopsyAdvantages over CT guided Biopsy

• Ability to sample lesions (including lymphAbility to sample lesions (including lymph nodes) too small to be identified by TUS, CT or MRICT or MRI

Mi i i i th i k f dl t k di• Minimizing the risk of needle track seeding

• Ability to obtain accurate local staging

Diagnostic Characteristics of EUS FNA gfor Pancreatic Mass Lesions

n Sensitivity (%) Specificity (%) A (%)Accuracy (%)

Giovannini [Endoscopy 1995;27(2)] 43 75 100 79

Cahn [AJS 1996;172(5)] 50 88 100 87

Bhutani [Endoscopy;1997;29(9)] 47 64 100 72

Chang [GIE;1997;45(5)] 44 92 100 95

Erickson [AFP 1997;55(6)] 28 -- --c so [ 99 ;55(6)] 896

Faigel [JClinOnc1997;15(4)] 45 72 100 75

Gress [GIE1997;45(3)] 121 80 100 85[ ; ( )]

Wiersema [Gastro 1997;112(4)] 124 87 100 88

Binmoeller [GIE1998;47(2)] 58 76 100 92

560 81% 100% 86%

Diagnosis by EUS FNADiagnosis by EUS FNA

• 102 patients with suspected pancreatic cancer p p pwith negative CT-guided FNA and/or ERCP sampling underwent EUS-FNAEUS FNA i i i 57 i (56%)• EUS-FNA was positive in 57 patients (56%)

• 4 patients who had a negative EUS-FNA subsequently were found to have pancreaticsubsequently were found to have pancreatic cancer

Gress F, et al. Endoscopic ultrasonography-guided fine needle aspiration biopsy of suspected pancreatic cancer. Ann Intern Med. 2001;134:459-64.

Follow up Study of EUS FNA Accuracy i S t d P ti CA ith iin Suspected Pancreatic CA with prior

negative CT/ERCP biopsies(Harewood et al Am J Gastro 2002 97(6)

185Subjects with known or suspected

58 36

Subjects with known or suspectedPancreatic Cancer

58Negative CT FNA

Biopsy

36Negative ERCPTissue Sampling

EUS FNAhad 90% sensitivity

for detecting malignancywith an overall 84% accuracy

EUS FNAhad 94% sensitivity

for detecting malignancywith an overall 92% accuracywith an overall 84% accuracy with an overall 92% accuracy

Lymph Node FNALymph Node FNALymph Node FNALymph Node FNA

Hitachi EUBHitachi EUB--60006000

Diagnostic Characteristics of EUS FNA forfor

Peri-intestinal Lymph Nodes

n Sensitivity (%) Specificity (%) Accuracy (%)

Bhutani [GIE 1997;45(6)] 22 100 100 100Bhutani [GIE 1997;45(6)] 22 100 100 100

Chang [GIE 1997;45(5)] 14 83 100 88

Erickson [AFP 1997;55(6)] 14 100 100 100

Gress [GIE 1997;45(3) 56 - - 93

Wiersema [Gastro 1997;112(4)] 192 92 93 92

Binmoeller [GIE 1998;47(2)] 43 91 100 95

Reed [AIS 1999;67(2)] 57 72 97 86

398 90% 98% 93%

Diagnosis by EUS FNADiagnosis by EUS FNA

• Molecular markers from EUS FNA can differentiate pancreatic neoplasia requiringdifferentiate pancreatic neoplasia requiring surgery from benign conditions and chronic pancreatitis (Anderson, et al)

• EUS FNA of pancreatic duct fluid in the l i f ievaluation of pancreatic cancer (Davila, et al)

Metastatic MelanomaMetastatic MelanomaMetastatic MelanomaMetastatic Melanoma

Bile Duct CancerBile Duct CancerCh l i iCh l i iCholangiocarcinomaCholangiocarcinoma

•• Difficult to see a mass with EUSDifficult to see a mass with EUS•• Difficult pathological diagnosis to Difficult pathological diagnosis to

make premake pre--operativelyoperativelypp p yp y•• Sensitivity of EUS with FNA is low ~ Sensitivity of EUS with FNA is low ~

60%60%60%60%

Staging Cholangiocarcinoma with EUSg g g

• Staging cholangiocarcinomas with EUS

• Role of intraductal US

EUS for Pancreatic NeoplasmsEUS for Pancreatic Neoplasms

D t l d i• Ductal adenocarcinoma– Diagnostic/Staging Accuracy– Negative Predictive Value

• Fine Needle Aspiration Biopsy• Neuroendocrine tumors• Miscellaneous: Lymphoma MetastasesMiscellaneous: Lymphoma, Metastases• Cystic Neoplasms

Normal Appearing PancreasNormal Appearing Pancreas

Negative Predictive Value of EUS f P i C ifor Pancreatic Carcinoma

Study Group

N NPV 95% CI

Kaufman 25 87% 60%-98%

Baron 32 88% 71% 96%Baron 32 88% 71%-96%

Brown* 74 96% 88%-99%

* 5-yr follow up; CA developed in 2 patientsEUS features of chronic pancreatitis

T1 Pancreatic Head CarcinomaT1 Pancreatic Head Carcinoma

16.3 mm x 13.1 mm

EUS for Detection of Pancreatic CCancer

• Panc CA: 4th leading cause of Ca death in• Panc CA: 4th leading cause of Ca death in men and women

• Overall 5-yr survival = 4%Overall 5 yr survival 4%• Survival is inversely proportionate to tumor

size• Small tumors, LN (-), Vascular Invasion (-) =

25% 5-yr survivalEUS i t CT/MR f l i 2• EUS superior to CT/MR for lesions < 2-cm

• Accurate detection of small lesions impacts timing and type of therapytiming and type of therapy

Ahmad et al. Amer J Gastroenterol 2001;96:2532-4.

T3 Pancreatic CancerT3 Pancreatic Cancer

EUS T-Staging AccuracyEUS T Staging Accuracy

Author # Staged # Surgical Staging AccuracyAuthor # Staged by EUS

# Surgical Patients

Staging Accuracy

Accuracy

Buscail 73 26 19/26 73%1999Gress1999

151 75 64/75 85%1999Ahmad2000

na 89 55/79 69%2000Total 190 138/180 77%*

* 95% CI = 70%-83%

EUS N-Staging AccuracyEUS N Staging Accuracy

Author # Staged by EUS

# Surgical Patients

Staging Accuracy

Accuracy

Buscail 73 26 18/26 69%Buscail 73 26 18/26 69%

Gress 151 71 51/71 72%

Ahmad na 89 35/67 54%

Total 186 104/164 63%*

* 95% CI = 56%-71%

EUS vs Helical CT for Pancreatic CCancer

DetectionAccuracy

fSensitivity

fSeries EUS CT EUS CT EUS CTLegman 27/27 25/27 20/22 19/22 6/7 7/7

Detection of resectabilit

for vascular

199827/27 25/27 20/22 19/22 6/7 7/7

Midwinter1999

33/34 26/34 25/30 23/30 13/16 9/16y invasion

Tierney2001

30/31 25/31 16/16 10/16Mertz 29/31 16/31 16/16 13/16 6/6 3/62000

29/31 16/31 16/16 13/16 6/6 3/6

Total 97%* 73% 91% 83% 91%* 64%

* P < 0.001When both EUS and MRI agree on resectability, 89% of cases were resectable

EUS Guided FNA for Pancreatic TTumors

• Sensitivity = 90%• Sensitivity = 90%• Specificity = 100%

Accuracy = 94%• Accuracy = 94%• For lesions as small as sub-cm• Yield is enhanced with on-site

cytopathologist• May require up to 3-5 passes• Biopsy primary, LNs, & liver lesions

Faigel et al. J Clin Onc 1997;15:1439-43Faigle et al. Diagn Cytopath 1998;18:98-109

EUS for Pancreatic N d i TNeuroendocrine Tumors

All Tumors Gastrinomas Insulinomas

N 75 36 36Sensitivity 93% 100% 88%Specificity 95% 94% 100%PPV 98% 95% 100%NPV 83% 100% 43%83% 100% 43%Accuracy 93% 97% 89%

Anderson, et al. AJG 2000;95:2271-7

Pancreatic LymphomaPancreatic Lymphoma

EUS for Non-Pancreatic Primary TTumors

• Lymphoma– FNA diagnosis with flow cytometry– Good prognosis– Directed therapy

• Metastases– BreastBreast– Renal Cell

Lewis et al. AJG 1998;93:834-6

OverviewOverview

• EUS– Anti-tumor therapyAnti-tumor therapy– Palliation of jaundice

Palliation of pain– Palliation of pain

EUS Guided radio-frequency or ETOH tumor ablation

Goldberg. GIE 1999;50:392Barclay. GIE 2002;55:266

Immune Therapy

Background• Tumors are immunosuppressive and block the host

immune responseimmune response

• Injection of lymphocyte culture (“Cytoimplant”) directly into tumors may block tumor immunosuppression and enhance host immune response

• Phase I study using Cytoimplant performed on pancreatic cancer showed extended survival and no toxicityy

Chang et al. Cancer 2000; 88:1325-1335

Phase II III Studies of CytoimplantPhase II-III Studies of Cytoimplant

ResultsResults• Multi center studyMulti center study

• Compared Cytoimplant to Gemcitibine

• Study stopped because interim analysis showed chemotherapy was better thanshowed chemotherapy was better than Cytoimplant

Viral Therapy-backgroundO 0 l hONYX-015 viral therapy

EUS- guided injection of Onyx 015 for pancreatic cancer

• 18 pts C it t itibi• Concomitant gemcitibine

• 3 minor responses (< 50% tumor reduction)

• 2 sepsis, 1 abscess, 2 duodenal p , ,perforations

Bedford et al. Gastointest Endosc 2000;51(4):AB 97

Gene TherapyTNFTNF-α

• TNF-α strong anti-tumor activity• TNF-α high toxicity with systemic administration• TNFarade-adenovirus vector carries the TNF-α gene• Gene promoter is radiation inducible• 37 Pts with locally advanced pancreatic Ca injected

with TNFarade followed by Chemo/XRT• Tumor stable or decrease in size in 74% at 3 mo

Chang KC. Gastrointest Endosc. 2004Farrell JJ. Gastrointest Endosc. 2006;63 AB93

Local ChemotherapyPaclitaxel (OncoGel)Paclitaxel (OncoGel)

• OncoGelW t l bl h d l– Water soluble hydrogel

– Releases paclitaxel continuously up to 6 weeks• Porcine model• EUS guided injection of OncoGel• High and sustained concentration in pancreas• No toxicity

Matthes K. GIE 2007;65:448

Palliation of JaundicePalliation of Jaundice

If ERCP fails, is there an alternative to PTC or surgical drainage?g g

Interventional EUSInterventional EUS

EUS-guided injection for diagnosisEUS guided injection for diagnosis

CholangiographyWiersema et. al., 1995 GIE,

PancreatographyGress et al 1996 GIEGress et. al., 1996 GIE

EUS GUIDED Hepatico-Gastrostomy

Panc. cancerPanc. cancer

Sahai GIE 1998;47:AB37Gastrointest Endosc. 2006 Jul;64:52

EUS GUIDED CHOLEDOCHO-DUODENOSTOMY

Kahaleh GIE 2004;60:138-42

What is the best way to palliate pain inWhat is the best way to palliate pain in pancreatic cancer?

Narcotics? or Celiac Plexus Block?

How about chronic pancreatitis?

Chronic Abdominal PainChronic Abdominal Pain

Can be a clinically challenging problem.Can be a clinically challenging problem.Management of chronic pain can be difficult There are many approaches to treating theThere are many approaches to treating the patient with chronic pain:- narcotic analgesianarcotic analgesia- celiac plexus block- surgery (ie; ganglionectomy)- surgery (ie; ganglionectomy)

Why CPB or CPN?Why CPB or CPN?

• Pain reliefPain relief• Palliative

I lit f lif• Improve quality of life

EUS-Guided Celiac Plexus Block andand

EUS-Guided Celiac Plexus N l iNeurolysis

Celiac Plexus BlockCeliac Plexus BlockCeliac Plexus BlockCeliac Plexus Block

Fi N dl A i tiFi N dl A i tiFine Needle AspirationFine Needle Aspiration

Celiac Plexus BlockCeliac Plexus BlockCeliac Plexus BlockCeliac Plexus Block

EUS Guided Celiac Plexus BlockEUS Guided Celiac Plexus Block

EUS-guided Celiac Plexus N l i f CNeurolysis for Cancer

58 patients58 patientspancreatic cancer

Follow-up 6 mo

• Pain score reduction in 78% of patients• Mean pain score decreased by 50%• Mean pain score decreased by 50%

Gunaratnam NT, GIE 2001;54:316

Relationship between pain and survival in pancreatic cancersurvival in pancreatic cancer

Pain correlates with resectability p=0 04Pain correlates with resectability p=0.04

Median Survival

• No pain before op 15 mo

Median Survival

No pain before op 15 mo• Pain before op 5.7 mo

P=0.003

Kelsen et al Surgery 1997;122(1):53-9

Effect of neurolysis on survival

137 pts randomized to intra-opneurolysis or placebo

• Neurolysis decreased pain scores and

neurolysis or placebo

• Neurolysis decreased pain scores and delayed or prevented onset of pain compared to placebo p<0 05compared to placebo p<0.05

• In patients with pre-operative pain, neurolysis improved survival compared to placebo p<0.0001p p

Lillemoe et al Ann Surg 1993;217(5):447-55

Effect of Neurolysis on Pain, Survival and Quality of LifeQuality of Life

100 Patients randomized to percutaneous celiac block or analgesic p.o. + sham block

• Pain reduction at 1 weekNeurolysis Analgesic

53% 27% P=.005

• % of patients with pain > 5/10• Survival at one year

14% 40% P=.005

16% 6% P=0.26

• Quality of life No difference

Wong GY et al. JAMA 2004:292:1092-99

Meta Analysis of 5 RCT-302 patients

Narcotic use at 2 and 8

wks

Yan BM. Am J Gastroenterol. 2007;102:430

Meta Analysis of 5 RCT-302 patients

Survival at8 wks

Yan BM. Am J Gastroenterol. 2007;102:430

CT vs. EUS CELIAC PLEXUS BLOCK FOR TREATMENT OF PAIN ASSOCIATED WITH

CHRONIC PANCREATITIS

Bupivacaine + Triamcinolone

CTN=8

EUSN=10

Pain benefit @ 8 wks 40% 25%

Pain benefit @ 24 wks 30% 12%Pain benefit @ 24 wks 30% 12%

Gress. Am J Gastroenterol 1999;94:872-4

EUS-guided celiac plexus block for chronic pancreatitischronic pancreatitis

90 patients

• 55% experienced significant improvement in pain

90 patients

score• Mean pain score @ 4 and 8 wks: 8 2 p< 0.05@• 26% experienced benefit > 12 wks• 10% experienced benefit > 24 wks• 10% experienced benefit > 24 wks

Age < 45 and prior pancreatic surgery predictedb fit t EUS G id d C li Bl kno benefit to EUS-Guided Celiac Block

Gress. Am J Gastroenterol 2001;96:409-16

Efficacy of EUS Guided Celiac Plexus Block (CPB) for Managing Abdominal Pain(CPB) for Managing Abdominal Pain

Associated with Chronic Pancreatitis (CP): A Meta-analysisA Meta-analysis

• Aim: To evaluate the efficacy of EUS-guided CPB in alleviating chronic abdominal pain in CP

• Method: A Medline database search was performed of the English literature for trials evaluating the efficacy of EUS-CPB for the management of chronic abdominal pain in CP

Efficacy of EUS Guided Celiac Plexus Block (CPB) for Managing Abdominal Pain

A i t d ith Ch i P titi (CP)Associated with Chronic Pancreatitis (CP): A Meta-analysis

• The diagnosis of CP was based on clinical presentation and a minimum of 4 EUS features of CP

• Studies involving less than 10-patients were excluded. • Data on pain relief was extracted, pooled, and analyzed.• A Bayesian hierarchical model for the meta analysis was• A Bayesian hierarchical model for the meta analysis was

developed. A Markov Chain Monte Carlo algorithm was implemented in the analysis.

• Results: 6 relevant studies were identified comprising a• Results: 6-relevant studies were identified comprising a total of 221 patients. EUS-guided CPB was effective in alleviating abdominal pain in 52.44% of patients (95% CI 31 64 74 9)31.64, 74.9).

Pain relief repo

Study

reported out of total patients

Observed proportion Analysis for proportion Quartiles

Estimates SE 95% CI 25% 50% 75%

Gress et al 1999 5/10 0.5 0.5037 0.1308 (0.2538 , 0.7556) 0.4117 0.5032 0.5958

Gress et al 2001 50/90 0.55 0.5539 0.0511 (0.4500 , 0.6517) 0.52 0.5565 0.5898

L t lLevy et al 2007 5/13 0.39 0.4099 0.1185 (0.1962 , 0.6508) 0.324 0.4075 0.4916

O’toole et al 2007 20/31 0.65 0.6314 0.0826 (0.4616 , 0.7831) 0.5762 0.6361 0.6873

LeBlanc et al 2007 27/51 0 53 0 5289 0 0681 (0 3959 0 6647) 0 4816 0 5279 0 57532007 27/51 0.53 0.5289 0.0681 (0.3959 , 0.6647) 0.4816 0.5279 0.5753

Stevens et al 2007 16/26 0.62 0.6025 0.0887 (0.4255 , 0.7661) 0.5423 0.6056 0.6641

Over All Studies 123/221 0.5244 0.1106 (0.3164, 0.7479) 0.449 0.5244 0.5994

Efficacy of EUS Guided Celiac Plexus Block cacy o US Gu ded Ce ac e us oc(CPB) for Managing Abdominal Pain

Associated with Chronic Pancreatitis (CP): A Meta-analysis

StudyGress 01Gress 99Levy 07O’toole 07LeBlanc 07Stevens 07

Summary

Observed0.55

0.50.390.65

530.62

Estimated0.55390.50370.40990.63140.52890.6025

0.52440.2 0.3 0.4 0.5 0.6 0.7

Efficacy of EUS Guided Celiac Plexus Block (CPB) for Managing Abdominal Pain

A i t d ith Ch i P titi (CP)Associated with Chronic Pancreatitis (CP): A Meta-analysis

ConclusionMeta-analysis demonstrates that EUS-guidedMeta-analysis demonstrates that EUS-guided CPB results in the reduction of abdominal pain due to CP in at least 50% of patients. pAppropriate patient selection and refinement in technique will likely lead to better results. Further prospective randomized trials are needed.

Conclusions• EUS

– Can deliver targeted anti-tumor therapies C id bili d ti d i– Can provide biliary and pancreatic drainage

– Celiac plexus neurolysis should be considered first line therapy for in pancreatic Ca paintherapy for in pancreatic Ca pain

– Celiac plexus block has a limited role in selected patients with chronic pancreatitis

• ERCP with Direct Cholangioscopy– Direct visualization

T t d bi– Targeted biopsy – Therapy

Unlimited opportunities for the future