Gastroenterology Grand Rounds - PowerPoint Presentation

Slide1

Gastroenterology Grand Rounds

January 22, 2015Fellow: David Tang, M.D.Faculty: Kal Patel, M.D.

Slide2

Case Presentation

65 year old woman

Presented to

Houston area hospital in

Sept 2013 with nausea, anorexia, and weight loss x 2 months

Jaundice x 1 week

Denied abdominal pain

Abdominal ultrasound showed

intrahepatic

biliary dilation

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CT Sept 2013

Slide4

Case Presentation

AST

111

ALT

125

Alk

Phos

341

Total Bilirubin

18.2

Direct Bilirubin

14.7

Total

Protein

6.9

Albumin

2.9

CEA

1.39

CA 19-9

< 1.00

Slide5

ERCP Sept 2013

Slide6

Case Presentation

Brush cytology

Unsatisfactory for evaluation

FNA cytology

Suspicious

Slide7

ERCP Nov 2013

Slide8

Case Presentation

Brush cytology

Negative (scant cellularity and poor preservation)

Intraductal

biopsy

No tissue identified

FNA cytology

Indeterminate (scant cellularity)

Slide9

Case Presentation

Diagnostic laparoscopy – December 2013

Cystic duct densely adherent to duodenum and porta

hepatis

with significant inflammation. No discrete mass was seen.

Patient then offered extended right

hepatectomy

for presumed malignancy.

Slide10

Case Presentation

Patient underwent portal venous embolization to optimize future liver remnant.

But after further consideration, patient decided against

hepatectomy

.

She was hospitalized in August 2014 with nausea and vomiting.

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EGD August 2014

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Case Presentation

Duodenal biopsy

Intestinal type mucosa with chronic inflammation

Duodenal stent was then placed

EUS with FNA was then repeated

Slide13

Courtesy of Dr. Zarrin-Khameh, Pathology

Slide14

Courtesy of Dr. Zarrin-Khameh, Pathology

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Diagnosis

Perihilar Cholangiocarcinoma (pCCA)

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Clinical Questions

Do advanced cytologic techniques improve diagnostic accuracy over brush cytology and transpapillary biopsy of pCCA?

What are the options for tissue diagnosis of

pCCA

beyond brush cytology and

transpapillary

biopsies?

How should these diagnostic modalities be integrated in the diagnosis of RFA?

Slide17

Classification of CCA

Intrahepatic CCA

Perihilar

CCA

Distal CCA

Extrahepatic

CCA

Slide18

Incidence of Extrahepatic CCA

Tyson Dig Dis

Sci

2014

Review of SEER registry from 1992 – 2007

However, before 1992,

pCCA

was not given unique ICD-O code. Between 1992 and 2000

pCCA

was only able to be linked to

iCCA

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The Problem with Tissue Diagnosis

Rizvi Gastro 2013

Slide20

Hattori BJS 2011

The Problem with Tissue Diagnosis

Slide21

Tamada

World J Gastroenterol

2011

Sensitivity

Specificity

Brush

Cytology

23 - 100%

100%

Transpapillary

Biopsy

5

2 – 83%

100%

The Problem with Tissue Diagnosis

Diagnostic uncertainty leads to delay in definitive treatment and repeated procedures are costly.

We should be familiar with our arsenal of diagnostic tools, including when and how to deploy them

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Advanced

Cytologic TechniquesFluorescence in situ Hybridization (FISH)

Moreno Gastro 2006

Trisomy

Diploid

Polysomy

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Advanced

Cytologic TechniquesDigitized Image Analysis (DIA)

Levy Am J

Gastroenterol

2008

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33 patients with biliary strictures underwent brush cytology, DIA, and FISH

Reference standard  surgical specimen or at least 9 months of follow upAdvanced

Cytologic

Techniques

Moreno Gastro 2006

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Advanced Cytologic Techniques

Barr

Fritcher

Am J

Clin

Pathol

2007

284

patients with biliary strictures underwent brush cytology, DIA, and

FISH

Reference standard

 surgical specimen or at least 6 months of follow up

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Single Operator Cholangioscopy

(SOC)

Victor World J

Gastroenterol

2011

Slide27

Single Operator Cholangioscopy

(SOC)

Manta

Surg

Endosc

2013

Study of 42 patients with biliary strictures who underwent

SpyGlass

with

SpyBite

Reference standard



surgical specimen or clinical follow up

18 patients with CCA

SpyBite

Sensitivity

Specificity

88%

94%

Slide28

Single Operator Cholangioscopy

(SOC)

Ramchandani

GIE 2011

SpyBite

biopsies in 33 patients with biliary stricture and previously inconclusive brush cytology and/or biopsy histology

Slide29

Endoscopic Ultrasound with Fine Needle Aspiration (EUS with FNA)

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Endoscopic Ultrasound with Fine Needle Aspiration (EUS with FNA)

Mohamadnejad

GIE 2011

74 patients with

extrahepatic

CCA who underwent EUS with FNA

Reference standard

 surgical specimen or unequivocal malignancy on cytology or clinical course

EUS with FNA

Overall Sensitivity

Sensitivity in proximal CCA

Sensitivity in distal CCA

79%

59%

81%

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Endoscopic Ultrasound

Fritscher

-Ravens Am J

Gastroenterol

2004

44 patients with potentially

resectable

hilar

masses suspicious for

pCCA

with previous negative brush cytology and/or histology

Reference standard

 surgical specimen

or

clinical

course

EUS with FNA

Sensitivity

Specificity

PPV

NPV

83%

100%

100%

57%

Slide32

Levy

Curr Opin Gastroenterol 2012

Incidence of tumor seeding is difficult to assess:

Tumor seeding may deposit cells that are undetected in the surgical specimen or deposited outside of field of resection

Inability to differentiate between tumor recurrence versus tumor seeding

EUS with FNA and Risk of Tumor Seeding

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Heimbach

HPB 2011191 patients with unresectable

pCCA

enrolled for

neoadjuvent

chemotherapy and radiation before liver transplant.

16 patients had trans-peritoneal FNA before

neoadjuvent

therapy

All patients had staging laparotomy after

neoadjuvent

therapy

Prevalence of metastasis

on laparotomy staging

Trans-peritoneal FNA

No FNA

6/16 (37.5%)

14/175 ( 8%)

EUS with FNA and Risk of Tumor Seeding

Slide34

Intraductal Ultrasound (IDUS)

Malignant



Heterogeneous

echo poor lesions with irregular

margins

Benign



Homogeneous

echo

rich

lesions with

smooth margins

Domagk Gut 2002

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Intraductal Ultrasound (IDUS)

Prospective study of 60 patients with biliary strictures undergoing IDUS

Reference standard



surgical specimen

Domagk Gut 2002

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Proposed Strategy for Tissue Diagnosis

Brush cytology + FISH or DIA and/or

Intraductal

Biopsy

Resectable

Non-

resectable

EUS FNA

Cholangioscopic

Biopsy

Surgical Specimen

IDUS

MRCP + CA 19-9

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Summary

Brush cytology may suffer from low diagnostic yield due to scant tumor cellularity and

desmoplasia

.

Advanced

cytologic

techniques (DIA and FISH) improve on cytology sensitivity.

Cholangioscopic

biospies

may be an option after negative brush cytology or

transpapillary

biopsy.

EUS with FNA results in improved sensitivity but suffer from risk of tumor seeding.

IDUS may be sensitive but cannot sample tissue

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Follow Up

Tumor board decision for chemotherapy follow by radiation.

Seen in Surgical Oncology clinic and deemed not a candidate for resection due to poor nutritional status and morbidity of

hepatectomy

and Whipple.

Slide39

EGD September 2014

Slide40

EGD September 2014

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Treatment of pCCA

Razumilava

Clin

Gastro

Hepatol

2013

Lobar hepatic resection with regional lymphadenectomy and

hepaticojejunostomy

Neoadjuvant

chemoradiation

followed by liver transplant

Tumor less than 3 cm in diameter

No metastasis

Unresectability

Systemic chemotherapy

Slide42

Photodynamic Therapy (PDT)

Ortner

Best

Pract

Res

Clin

Gastroenterol

2004

Photosensitizer is administered via IV and accumulates preferentially in tumor tissue

Tumor is exposed to light of a certain wavelength which activates photosensitizer resulting in damage to tumor tissue

Depth of necrosis is between 4 to 6 mm

Major side effect of systemic photosensitivity

Slide43

Photodynamic Therapy (PDT)

Ortner

Gastro 2003

Randomized controlled trial between 31 patients with

unresectable

CCA randomized to stenting alone vs stenting + PDT.

Median survival time was 493 days in stenting + PDT group compared with 98 days in stenting only group (p < 0.0001).

Slide44

Intraductal Radiofrequency Ablation

Dolak

Surg

Endosc

2013

Slide45

Intraductal Radiofrequency Ablation

Dolak

Surg

Endosc

2013

58 patients treated with

intraductal

RFA over two years.

Overall, median survival

was 10.6

months from

the time of the

first RFA

and 17.9

months from

the time of initial

diagnosis.

The

median stent patency after the last electively performed RFA was 170 days

and

was almost

significantly

different between metal and plastic stenting (218

vs

.

115

days;

p = 0.051)

One major complication of partial liver infarction thought to be thermal injury of a hepatic artery

Slide46

FISH and DIA in Negative Cytology and Histology

Levy Am J

Gastroenterol

2008

Slide47

Courtesy of Dr. Zarrin-Khameh, Pathology