Transcript Week 14

Gastrointestinal Cancers
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Pancreatic Cancer
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Breast Cancer
New diagnoses each year in the US:
246,660 Women
2,600 Men
40,450 estimated deaths from breast cancer in 2016
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Pancreatic Cancer
New diagnoses in 2015 (US):
48,960
40,560 died of pancreatic cancer in 2015
6.9% of all cancer deaths, and the 4th
leading cause of cancer deaths in the U.S.
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Incidence by Race & Gender
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Breast Cancer
Lifetime Risk: 1/8.1 Women
Median age of diagnosis = 61 YOA
Median age of death = 68 YOA
5 year survival = 89.4%
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Pancreatic Cancer
Lifetime Risk: 1/67
Median age of diagnosis = 71 YOA
Median age of death = 73 YOA
5 year survival = 7.2%
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• Endocrine function:
Islet cells secrete glucose-regulating hormones
• Exocrine function (98%):
Acinar cells secrete digestive enzymes
The most common (~95%) type of pancreatic
cancer is exocrine—i.e., adenocarcinoma.
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Risk Factors
Diabetes
Smoking
Obesity
Chronic Pancreatitis
Family History
Heritable disorders
e.g., HNPCC; von Hippel-Lindau syndrome, Peutz-Jeghers syndrome.
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Symptoms
Early: None
Later in the disease:
Dark urine/pale stool
Stool that floats
Jaundice
Upper abdominal pain
Continual middle back pain
Fatigue/weakness
Loss of appetite/unexplained weight loss
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Staging
Stage 1: Tumor confined to the pancreas.
IA: < 2cm
IB: > 2cm
Stage 2: Cancer has spread to nearby organs, (via lymphatics or
shedding) but not to the local blood vessels.
IIA: spread to local organs but NOT lymph nodes
IIB: spread to regional lymph nodes; maybe to local organs
Stage 3: Cancer has invaded to local blood vessels (e.g., superior
mesenteric artery, celiac axis, common hepatic artery, and portal
vein). Lymph nodes may be involved.
Stage 4: Cancer is found at distant sites.
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Physical Exam
Diagnosis
CT
Ultrasound
Endoscopy (EUS, ERCP, PCT)
MRI
PET Scan
Blood Tests (chemistry, CA 19-9, CEA)
Needle Biopsy
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Laparoscopy
Surgical Treatment
Whipple: (Body/tail left
intact, head, part of
stomach, part of small
intestine, gallbladder
removed)
Pancreatectomy (pancreas
along with part of stomach,
part of small intestine,
spleen, gallbladder removed)
Distal pancreatectomy
(Head left intact,
body/tail/spleen removed)
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Whipple Procedure
Operative mortality = 1-16%
2-3 week hospital stay
1-3 months’ rest at home
4-6 weeks of difficulty digesting food (full and bloated feeling)
Digestion problems should dissipate after 3 months
5 year survival: 18-24%
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Other Treatment
Chemotherapy
Radiation Therapy
Targeted Therapy
(EGF-R kinase inhibitor [Tarceva])
Pain Control
(pharmaceutical, epidural, acupuncture/hypnosis)
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Colorectal Cancer
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Colorectal Cancer
New diagnoses in 2015 (US):
132, 700
49,700 died of colorectal cancer in 2015
2nd leading cause of cancer deaths in the
U.S.
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Incidence by Race & Gender
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Colorectal Cancer
Lifetime Risk: 1/22
(4th most common)
Median age of diagnosis = 68 YOA
Median age of death = 73 YOA
5 year survival = 64.9%
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Risk Factors
Age > 50
Smoking
IBD (ulcerative colitis)
HNPCC (hereditary non-polyposis colon cancer (2%))
Familial adenomatous polyposis (<1%)
Other solid tumors (breast, ovarian)
High fat, low fiber diet
Personal History of polyps
Family History
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Family History
Family History
No family history
Relative Risk for
CRC
Absolute Risk of CRC by
Age 79 yoa
1
4%
One first-degree relative with CRC
2.3
9%
More than one first-degree relative with CRC
4.3
16%
One affected first-degree relative diagnosed with CRC
before age 45 y
3.9
15%
One first-degree relative with colorectal adenoma
2.0
8%
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Symptoms
Early: None
Later in the disease:
Bloody stool
‘Narrow’ stool
Diarrhea or Constipation
Gas Pains/bloated feeling
Fatigue/weakness
Nausea or vomiting
Loss of appetite/unexplained weight loss
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Staging
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Stage 0: Carcinoma in situ
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Stage 1: Tumor is confined to the inner colon wall.
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Stage 2: Tumor has invaded deeper into the colon wall, and possibly nearby
tissues, but has not disseminated to the lymph nodes.
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Stage 3: Cancer has disseminated to local lymph nodes but not to distant sites.
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Stage 4: Cancer is found at distant sites.
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Survival
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Screening/Diagnosis
Physical Exam
Fecal Occult Blood Test
Sigmoidoscopy
Colonoscopy
X-rays (Barium)
Digital Rectal Exam
“Virtual Colonoscopy” (CT)
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Camera Capsule
Carcinoembryonic Antigen (CEA)
CEA is elevated in patients with colorectal cancer,
but clinical trials show that there are too many
false positives. Therefore, this test should not be
the sole indicator used to diagnose cancer.
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Surgical Treatment
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Surgery
Treatment
Cryosurgery
Radiofrequency Ablation
Chemotherapy
Radiation Therapy
Biological Therapy
(e.g., Avastatin—anti-angiogenic agent)
Targeted Therapy
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(e.g., Regorafinib—multi kinase inhibitor)
(e.g., anti EGF-R, VEGF-R2 monoclonal antibodies)
Stomach Cancer
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Stomach Cancer
New diagnoses in 2015 (US):
24, 590
10,720 died of colorectal cancer in 2015
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Incidence by Race & Gender
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Stomach Cancer
Lifetime Risk: 1/111
Median age of diagnosis = 69 YOA
Median age of death = 72 YOA
5 year survival = 29.3%
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Risk Factors
Helicobactor pylori infection
Chronic gastritis
Intestinal metaplasia (reflux)
Familial adenomatous polyposis
Diet high in salted & smoked foods, low in fruits & vegetables
Eating improperly cooked or stored foods
Smoking
Family History
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Symptoms
Early:
Indigestion and stomach discomfort
A bloated feeling after eating
Mild nausea
Loss of appetite
Heartburn
Later in the disease:
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Blood in the stool
Vomiting
Unexplained weight loss
Stomach pain
Jaundice
Abdominal Ascites
Difficulty swallowing
Diagnosis
History and Physical Examination
Blood tests (e.g., CBC, CEA)
Endoscopy (upper, EUS)
X-ray (Barium swallow)
CT
PET Scan
Biopsy
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Stage 0: Carcinoma in situ
Staging
Stage 1: Minimally-invasive mucosal tumor
Stage IA: mucosal and submucosal involvement
Stage IB: mucosal, submucosal and 1-2 lymph nodes OR
muscle layer involvement,
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Staging (cont’d)
Stage 2: Invasive Mucosal tumor
Stage IIA: Submucosal layer involvement and 3-6 lymph nodes OR
Muscle layer involvement and 1-2 lymph nodes OR
Involvement of the sub-serosa
Stage IIB: Submucosal layer involvement and 7+ lymph nodes OR
Involvement of the sub-serosa and 1-2 lymph nodes OR
Serosal involvement
Stage 3: Cancer has disseminated to local lymph nodes but not to distant sites.
Stage IIIA: Muscle layer involvement and 7+ lymph nodes OR
Serosal involvement and 1-2 lymph nodes OR
Involvement of the sub-serosa and 3-6 lymph nodes
Stage IIIB: Serosal involvement and 3-6 lymph nodes OR
Involvement of the sub-serosa and 7+ lymph nodes OR
Tumor has spread to nearby organs (e.g., kidney, spleen, pancreas)
and 1-2 lymph nodes
Stage IIIC: Serosal involvement and 7+ lymph nodes OR
Tumor has spread to nearby organs and 3+ lymph nodes
Stage 4: Cancer is found at distant sites.
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Survival
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Treatment
Surgery
(gastrectomy [partial or total], endoluminal stent or
laser therapy)
Chemotherapy
Radiation therapy
Targeted therapy
(e.g., anti Her-2, VEGF-R2 monoclonal antibodies)
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Gastrointestinal Stromal Tumors (GISTs)
May be malignant or benign
Tumors anywhere in the GI tract, but most common in the stomach and small
intestine
May originate in Interstitial Cells of Cajal (ICC)
Small GISTs are very common
Hereditary predilection (NF-1 gene mutation)
Signs of gastrointestinal stromal tumors include blood in the stool or vomit.
Diagnosis via CT, MRI or endoscopy
Biopsy determines “mitotic rate”
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Surgical treatment + Gleevec (c-kit kinase inhibitor)
Liver Cancer
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Hepatocellular & Bile Duct Cancer
New diagnoses in 2015 (US):
35, 660
24,550 died of liver and intrahepatic bile duct cancer in 2015
Although Hepatocellular cancer ranks 13th in the U.S. for cancerrelated deaths, it is the 3rd leading cause world wide.
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Incidence by Race & Gender
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Hepatocellular and Bile Duct Cancer
Lifetime Risk: 1/111
Median age of diagnosis = 63 YOA
Median age of death = 67 YOA
5 year survival = 17.2%
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Risk Factors
Hepatitis infection
Cirrhosis
Consumption of Aflatoxin
Hemochromatosis
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Symptoms
A hard lump on the right side just below the rib cage
Discomfort in the upper abdomen on the right side
A swollen abdomen
Referred pain near the right shoulder blade or in the back
Jaundice
Easy bruising or bleeding
Weakness or fatigue
Nausea and vomiting
Loss of appetite or feelings of fullness after eating a small meal.
Unexplained weight loss
Pale, chalky bowel movements and dark urine
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Fever
Diagnosis
History and physical exam
Serum alpha-fetoprotein (AFP)
(Other cancers and certain noncancerous conditions, including cirrhosis
and hepatitis, may also increase AFP levels. Sometimes the AFP level is
normal even when there is liver cancer.)
Liver function tests
CT scan
MRI
Ultrasound
Biopsy
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(Fine- or Core-needle aspiration biopsy or biopsy by Laparoscopy)
The Barcelona Clinic Liver Cancer
Staging System
Stage 0: Very early
Stage A: Early
Stage B: Intermediate
Stage C: Advanced
Stage D: End-stage
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Treatment
Depends upon Stage
BCLC stages 0, A, and B: Treatment goal is to cure the cancer.
BCLC stages C and D: Treatment goal is to relieve the symptoms caused by
liver cancer and improve the patient's quality of life Treatments are not
likely, nor are intended to cure the cancer.
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Treatment
Surveillance
Surgery
(e.g., partial hepatectomy or Liver transplant)
Chemotherapy
Radiation Therapy
Ablation therapy
(e.g., Radiofrequency ablation, percutaneous ethanol injection,
cryoablation, microwave therapy)
Embolization therapy
(e.g., Trans-arterial embolization, trans-arterial
chemoembolization)
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Targeted therapy
(e.g., Sorafenib [kinase inhibitor])