Fernando 12-18-07 Gi Malignancies

Front 1

Objectives:

clinical presentation

work-up

treatment

Back 1

-

Front 2

Overall, colon and rectum cancer is case for what fraction of cancer death

Back 2

10% Second leading cause

Front 3

There is a link between colon cancer and consumption of what type of food?

Back 3

fat

Front 4

a common cause of microcytic anemia

Back 4

iron deficiency

(maybe normal in women, never normal in men)

Front 5

presentation and workup of colon cancer given in class

Back 5

fatigue and shortness of breath
Complete blood count: Hgb 8.5, Hct 27%, MCV 75, WBC 8.0, Plt 250K
Previous year: Hgb 15, Hct 45%, MCV 90

Stool cards positive for occult blood
Colonoscopy with large mass at sigmoid colon

Front 6

management of colon cancer

Back 6

Polypectomy (Limited to small lesions)
Surgical resection
-Hemicolectomy
-en bloc lymph node dissection (15nodes)
-Colostomy may be required

Front 7

Dukes staging

Back 7

A - invasion thru muscularis propria
B - thru serosa
C - regional nodes
D - apical nodes

Front 8

T - The degree of invasion of the intestinal wall
T0 - no evidence of tumor
Tis- cancer ______ (tumor present, but no invasion)
T1 - invasion through __________ into lamina propria (basement membrane invaded)
T2 - invasion into the muscularis _______
T3 - invasion through the muscularis propria OR to adjacent ______
T4 - invasion completely through the wall of the _____

Back 8

T - The degree of invasion of the intestinal wall
T0 - no evidence of tumor
Tis- cancer in situ (tumor present, but no invasion)
T1 - invasion through submucosa into lamina propria (basement membrane invaded)
T2 - invasion into the muscularis propria
T3 - invasion through the muscularis propria OR to adjacent mucosa
T4 - invasion completely through the wall of the colon

Front 9

N - the degree of lymphatic node involvement
N0 - no lymph nodes involved
N1 - one to _____ nodes involved
N2 - ____ or more nodes involved

Back 9

N - the degree of lymphatic node involvement
N0 - no lymph nodes involved
N1 - one to three nodes involved
N2 - four or more nodes involved

Front 10

M - the degree of metastasis
M0 - __ metastasis
M1 - metastasis _______

Back 10

M - the degree of metastasis
M0 - no metastasis
M1 - metastasis present

Front 11

Stage IV
Any T, Any N, M_

Back 11

Stage IV
Any T, Any N, M1

Front 12

Stage IIIA
T1, N_, M0
T2, N_, M0
Stage IIIB
T_, N1, M0
T_, N1, M0
Stage IIIC
Any T, N_, M_

Back 12

Stage IIIA
T1, N1, M0
T2, N1, M0
Stage IIIB
T3, N1, M0
T4, N1, M0
Stage IIIC
Any T, N2, M0

Front 13

Chemotherapy alone for most colon cancers

Radiation therapy plus chemotherapy for ______ cancers

Back 13

Chemotherapy alone for most colon cancers

Radiation therapy plus chemotherapy for rectal cancers

Front 14

Chemotherapy reduced recurrence by __% in both early and late stage colon ca cases, but absolute benefits markedly different (24% versus 2%)

Back 14

Chemotherapy reduced recurrence by 40% in both early and late stage colon ca cases, but absolute benefits markedly different (24% versus 2%)

Front 15

What tumor marker is found with colon cancer?

Back 15

CEA

Front 16

Common locations of metastatic disease include _____, ____ and ____

Back 16

Common locations of metastatic disease include liver, lung and bone

Front 17

_________________ Remain the Cornerstone of CRC Management

Back 17

Fluoropyrimidines Remain the Cornerstone of CRC Management

Front 18

____: A Key Mediator of Angiogenesis

potent stimulator

Back 18

VEGF: A Key Mediator of Angiogenesis

potent stimulator

Front 19

anti-VDGF antibody

Back 19

Avastin® (bevacizumab)

Recombinant humanized monoclonal IgG1 antibody1

Front 20

Common locations of metastatic disease include _____, ____ and ____

Back 20

Common locations of metastatic disease include liver, lung and bone

Front 21

_________________ Remain the Cornerstone of CRC Management

Back 21

Fluoropyrimidines Remain the Cornerstone of CRC Management

Front 22

____: A Key Mediator of Angiogenesis

potent stimulator

Back 22

VEGF: A Key Mediator of Angiogenesis

potent stimulator

Front 23

anti-VDGF antibody

Back 23

Avastin® (bevacizumab)

Recombinant humanized monoclonal IgG1 antibody1

Front 24

Early detection
FOBT reduces mortality 33%

FOBT = ____ ______ ______ testing

Back 24

Early detection
FOBT reduces mortality 33%

FOBT = fecal occult blood testing

Front 25

~_-_% of all cases of CRC are hereditary
~15-20% are “familial” / multifactorial
~75% of cases are _______

Back 25

~5-8% of all cases of CRC are hereditary
~15-20% are “familial” / multifactorial
~75% of cases are sporadic

Front 26

Hereditary CRC syndromes

Back 26

Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
Familial Adenomatous Polyposis (FAP)


Multiple adenomatous polyposis syndrome/MYH gene (MAP)
Peutz-Jeghers syndrome (PJS)
Familial Juvenile Polyposis (FJP)

Front 27

HNPCC: AKA

Back 27

“Lynch syndrome”

Front 28

HNPCC: Clinical Diagnostic Criteria

Amsterdam II Criteria (3-2-1 rule)
No point memorizing

Back 28

HNPCC: Clinical Diagnostic Criteria

Amsterdam II Criteria (3-2-1 rule)

3 or more relatives with an HNPCC-related cancer, one of whom is a 1st degree relative of the other two
2 or more successive generations affected
1 or more cancers diagnosed before age 50

Front 29

______________ Instability (MSI) on tumor tissue
can be used to screen for HNPCC in select cases
____________________ (IHC) on tumor tissue
can be used to detect the presence or absence of the mismatch repair proteins (MSH2, MLH1, etc.)

Back 29

Microsatellite Instability (MSI) on tumor tissue
can be used to screen for HNPCC in select cases
Immunohistochemistry (IHC) on tumor tissue
can be used to detect the presence or absence of the mismatch repair proteins (MSH2, MLH1, etc.)

Front 30

Proceed Directly To Genetic Testing After genetic counseling and informed consent!
IF:

Back 30

Family history fulfills Amsterdam II criteria or
Patient has two HNPCC related cancers or
Patient has CRC and a 1st degree relative with HNPCC-related cancer, with at least one cancer diagnosed <50 years of age
Always test an affected family member first!

Front 31

Who is average risk pt for CRC?

Back 31

No FH or 1-2 distant relatives with CRC.

Front 32

What CRC management do you do for avg CRC pt

Back 32

At age 50:

FOBT annually + Flex sig every 5 yrs; OR
- Colonoscopy every 10 yrs; OR
- DCBE every 5 yrs

Front 33

CRC Risk Management for moderate risk pt. When do you start?

Back 33

age 40 ( or 5-10 yrs earlier than earliest case in family)

Front 34

CRC Risk Management for HNPCC or suspected HNPCC pt. When do you start?

Back 34

20-25

Front 35

CRC Risk Management for FAP or suspected FAP pt. When do you start?

Back 35

10-12

Front 36

Site of most adenocarcinomas in the esophagus

Back 36

GE junx

(Barrett's)

Front 37

Risk factors for squamous cell
)

Back 37

Risk factors for squamous cell
Tobacco
EtOH
Other toxins (Beetle nut, nitrosamines)

Front 38

Risk factors for adenocarcinoma

Back 38

Risk factors for adenocarcinoma
GERD
Obesity

Front 39

most common presenting symptom (75%)
of esophageal cancer

Back 39

Dysphagia
initially solids, but eventually include liquids

Weight loss (50-60%)
Hoarseness (recurrent laryngeal nerve)
Respiratory symptoms from aspiration or tracheobronchial fistula

Front 40

work-up of EC

Back 40

endoscopy and/or barium swallow (staging)
Endoscopic Ultrasound
PET Scan

Front 41

Neoadjuvant therapy

Back 41

before surgery

Front 42

R0 resection?

Back 42

no positive margins

Front 43

Barrett’s Esophagus

Squamous epithelium of the esophagus replaced by ________ epithelium (__________ metaplasia)
Develops in 5-8% of patients with ____
Endoscopy is indicated for severe symptoms

Considered a precursor lesions of esophageal ______________

Back 43

Barrett’s Esophagus

Squamous epithelium of the esophagus replaced by columnar epithelium (intestinal metaplasia)
Develops in 5-8% of patients with GERD
Endoscopy is indicated for severe symptoms

Considered a precursor lesions of esophageal adenocarcinoma

Front 44

4th most common cause of cancer death in the US

Back 44

pancreas

Front 45

Genetic predisposition for pancreatic cancer(5%)

Back 45

Hereditary pancreatitis, familial pancreatic ca
p16, BRCA2 mutations, MEN, HPNCC, etc.

Front 46

Vast majority of pancreatic tumors are ___crine tumors and _____carcinomas
Other ___crine tumors include giant cell and cystic neoplasms

Back 46

Vast majority of pancreatic tumors are exocrine tumors and adenocarcinomas
Other exocrine tumors include giant cell and cystic neoplasms

Front 47

Endocrine tumors
Islet of Langerhans: G_______oma, I______oma S___________oma, G______oma
C________ - rare

Back 47

Endocrine tumors
Islet of Langerhans: Glucagonoma, Insulinoma Somatostatinoma, Gastrinoma
Carcinoid - rare

Front 48

Presentation of pancreatic cancer

Back 48

Symptoms are generally non-specific
Anorexia, malaise, nausea, fatigue, epigastric or back pain
Weight loss
New onset diabetes
Migratory thrombophlebitis (Trousseau sign)
Jaundice – frequent presenting complaint in pancreatic head lesions

Front 49

Initial management of jaundice may require placement of a _____ for fever or infectious symptoms
ERCP (endoscopic chalangiopancreatography)
-Initial diagnosis via brushings
-Placement of stent
Percutanoues Billiary Stent
Distal obstructions
Internal/external stents

Back 49

Initial management of jaundice may require placement of a stent for fever or infectious symptoms
ERCP (endoscopic chalangiopancreatography)
Initial diagnosis via brushings
Placement of stent
Percutanoues Billiary Stent
Distal obstructions
Internal/external stents

Front 50

Treatment Options for pancreatic cancer

Back 50

Staging for pancreatic cancer continues to evolve and still centers on “resectable” vs “nonresectable”
Surgical approaches differ for masses in the head, body, tail, or uncinate process of the pancreas

**Surgery is the Only curative modality

Front 51

Location of tumor determines operation
Body/Tail: partial pancreatectomy
Head: Whipple (pancreatico______ectomy)

Back 51

Location of tumor determines operation
Body/Tail: partial pancreatectomy
Head: Whipple (pancreaticoduodenectomy)

Front 52

Drug for adjuvant preacreatic cancer therapy

Back 52

gemcitabine

Front 53

Factors contributing to sporadic (nonhereditary) RCC include s______, o______, and environmental toxins
Hereditary factors also contribute to RCC
Mutation of the ___ gene is inherited in most cases of ___ disease and can lead to RCC

Back 53

Factors contributing to sporadic (nonhereditary) RCC include smoking, obesity, and environmental toxins
Hereditary factors also contribute to RCC
Mutation of the vHL gene is inherited in most cases of vHL disease and can lead to RCC

Front 54

presentation of RCC

Back 54

Classic triad:
Hematuria, flank pain and abdominal mass
Metastatic symptoms
Bone pain, adenopathy, pulmonary mets
Paraneoplastic syndromes
Hypercalcemia, erythrocytosis, liver dysfunction
Other
Weight loss, Anemia, varicocele
Often incidental finding on unrelated imaging

Front 55

Management of RCC

Back 55

Initial assessment with renal protocol CT and/or MRI
Biopsy historically has been avoided
Risk of seeding
Non-diagnostic results
With non-surgical treatments available, biopsies are being reconsidered

Surgical resection only effective therapy
Radical nephrectomy: complete removal of Gerota fascia, perirenal fat, +/- adrenal gland, +/- lymph node dissection
Nephron sparing: unilateral kidney, inadequate contralateral function, small tumors
Radiofrequency or cryoablation for selected patients
Renal vein or IVC involvement not a contraindication to surgery
50% long term survivors
Nephrectomy may be indicated in presence of limited or extensive metastatic disease

Front 56

Adjuvant therapy for RCC?

Back 56

Historically has had no role
Randomized trials of interferon and IL-2 have been negative
Given substantial activity of tyrosine kinase inhibitors, phase III adjuvant trials are ongoing

Front 57

von Hippel-Lindau Disease

Autosomal dominant cancer syndrome
Characterized by predisposition to develop highly vascular tumors such as ___ as well as other tumors (adrenal, brain, and pancreas)
Caused by inactivation of vHL tumor suppressor gene
vHL gene mutation occurs in over 50%-80% of spontaneous RCCs
The vHL gene product (pVHL) regulates VEGF levels; mutation of the vHL gene results in
Increased transcription of the VEGF gene
Increased stability of VEGF mRNA

Back 57

von Hippel-Lindau Disease

Autosomal dominant cancer syndrome
Characterized by predisposition to develop highly vascular tumors such as RCC, as well as other tumors (adrenal, brain, and pancreas)
Caused by inactivation of vHL tumor suppressor gene
vHL gene mutation occurs in over 50%-80% of spontaneous RCCs
The vHL gene product (pVHL) regulates VEGF levels; mutation of the vHL gene results in
Increased transcription of the VEGF gene
Increased stability of VEGF mRNA

Front 58

Antibody that Recognizes all isoforms of VEGF

Back 58

Bevacizumab

Front 59

What drug?

Orally administered tyrosine kinase inhibitor
Inhibits VEGF and PDGF
Phase III trial compared first line treatment with sunitinib versus interferon
Response rate higher with sunitinib
31% versus 6%
Progression free survival prolonged
11 months versus 5 months

Back 59

Sunitinib

Front 60

Oral tyrosine kinase inhibitor
Targets: VEGF, PDFG, c-KIT, RET
Compared to placebo in patients with progression on first line therapy
Response 2%, stable disease 78%
Placebo: Response 0%, stable disease 55%

Back 60

Sorafenib (Nexavar)