Transcript Cancer – the Essentials

Cancer – the Essentials
Michele Ritter, M.D.
Argy Resident – February, 2007
Risk Factors for Cancer
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Breast
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Colon
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Tobacco
Ionizing Radiation
Asbestos (with tobacco)
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Esophagus
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Tobacco
Alcohol
Barrett’s esophagus
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Tobacco
Schistosoma haematobium
Aromatic amine exposure
Cervical
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Hep. C, Hep. B
Aflatoxin
Vinyl chloride
Alcohol (cirrhosis)
Urinary Bladder
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Asbestos
Family history
Hepatocellular (liver)
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Tobacco
Prostate
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Nulliparity
Pancreas
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Pleura/Mesothelioma
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Family History
Inflammatory Bowel Disease
Ovary
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Lung
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Early menarche, nulliparity, or late first
full-term pregnancy
Exogenous estrogens
Ionizing radiation
Family History
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Human Papillomavirus
Endometrial
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Obesity
Exogenous, unopposed estrogen
Diabetes mellitus
Low parity
Cancer Prevention
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Lung Cancer
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Smoking cessation!!!
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Tobacco is related to lung, head and neck, esophagus,
pancreas, bladder, kidney, stomach and possibly colon and
uterine cancers
Second hand smoke has been shown to be risk factor for
lung cancer
Smoking Cessation
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The 5 “A’s” for smoking cessation
1.
2.
3.
4.
Ask: Systematically identify all tobacco users at
every visit
Advise: Strongly urge all tobacco users to quit
Assess: Determine a patient’s willingness to
attempt to quit
Assist: Aid the patient in quitting.
1.
5.
Includes counseling, pharmacotherapy, social support
Arrange: Schedule follow-up contact.
Smoking Cessation (cont.)
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Pharmacotherapy
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Nicotine Replacement
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Bupropion (Zyban)
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Design to ameliorate symptoms of nicotine withdrawal: anxiety, dysphoria
or depressive symptoms, insomnia, increased appetite/weight gain,
Includes gum, patches, nasal spray, inhaler
Enhance noradrenergic, dopaminergic function
Also used as an anti-depressant (Wellbutrin)
Has been shown to significantly increase rate of smoking cessation
(especially when used in combination with nicotine replacement).
Caution in anorexic/bulemics (increased rate of seizures)
Varenicline
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Is a partial agonist of nicotine acetylcholine receptor
Has been shown to increase rate of quitting (may even be better than
bupropion)
Cancer Prevention (cont.)
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Breast Cancer
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Tamoxifen therapy
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Shown to be beneficial in women who have at least a 1.7% absolute
risk of developing the disease over the subsequent 5-year period
(http://bcra.nci.nih.gov/brc)
At 20 mg/day for 5 years , a decreased risk for invasive and
noninvasive cancer of 50% was seen.
Caution:
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Increased risk for endometrial cancer
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Increased risk for life-threatening thromboembolic events
No evidence yet showing that prophylactic mastectomy,
oophorectomy is beneficial woman with average risk.
Limit exposure to postmenopausal hormone replacement therapy
Cancer Prevention (cont.)
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Colon Cancer
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Possible benefit with NSAID use (specifically in
patients with familial adenomatous polyposis) –
but not yet recommended routinely.
Gastric Cancer
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Antibiotic eradiation of Helicobacter pylori
-carotene, vitamin E, selenium supplementation
(in Chinese)
Cancer Prevention
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Prostate Cancer
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Finasteride
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A 5- reductase inhibitor, blocks conversion of
testosterone to dihydrotestosterone.
Show to decrease the risk for prostate cancer in men
aged 55 years and older (but mortality was equal)
Decreased urinary symptoms with finasteride
Cancer Prevention
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Diet
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While increased fruits and vegetables have been
found to decrease cardiovascular disease, there
has been no significant benefit seen in cancer
prevention with fruits/vegetables.
Cancer Screening
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Cervical Cancer
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Pap Smear
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Beginning when patient becomes sexually active until
age 65 (or until total hysterectomy)
At least every 3 years.
Insufficient evidence to screen routinely for human
papillomavirus (HPV)
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HPV-DNA testing as follow-up if low-grade atypia or other
abnormalities found..
Cancer Screening (cont.)
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Breast Cancer
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Mammogram
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Once every 1 to 2 years age 40-49 years
Annual mammogram for age ≥ 50
Breast exam
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Either performed by patient or provider, has not been
found to have any effect on outcome.
Cancer Screening (cont.)
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Colon Cancer
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Beginning at age ≥ 50
Colonoscopy, flexible sigmoidoscopy, fecal
occult blood testing, barium enema used alone or
in combination are equally effective.
If family history of colon cancer in first degree
relative, first colonoscopy 10 years prior to
his/her age at diagnosis.
Cancer Screening (cont.)
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Prostate Cancer
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Skin Cancer
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Routine screening for skin cancer using a total body skin exam not
recommended.
Ovarian Cancer
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USPSTF has not found evidence supporting the routine use of PSA.
Also has not found that routine DRE is helpful.
Does not recommend vaginal ultrasound or CA-125 measurement
Lung Cancer
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No established guidelines yet for the use of screening CT of the chest
Oncologic Complications
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Hypercalcemia
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The most common
metabolic paraneoplastic
syndrome
Seen in:
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Squamous cell carcinoma
(lung, head, neck)
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Frequently produce PTHrP
Multiple myeloma
Breast carcinoma
T-cell lymphoma
Renal Cell carcinoma
Symptoms:
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Confusion
Fatigue
Constipation
Nausea
Polyuria
Management
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Vigorous hydration
Lasix
Bisphosphonates
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Pamidronate
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Zoledronic acid
Oncologic Complications
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Superior Vena Cava
Syndrome
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Swelling face, neck, arms
(especially when patient is supine)
Cough
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Dyspnea
Hoarseness due to laryngeal edema
Headaches (increased intracranial
pressure)
Most commonly occurs in
Lung Cancer (small cell)
Lymphoma (Hodgkin and nonHodgkin)
Mediastinal germ cell tumors
Exam:
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Symptoms
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Periorbital and arm
edema
Elevated JVP
Increased number of
collateral veins covering
anterior chest wall
Diagnosed via: CT scan
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Should show right hilar
mass with SVC
occlusion
An oncologic urgency
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Tissue diagnosis
recommended
Radiation therapy (or
chemo. if small cell or
lymphoma)
Oncologic Complications
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Spinal Cord Compression
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New or significantly worsening
back pain/tenderness with
neurologic deficits.
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Urinary incontinence, fecal
incontinence
Lower extremity weakness
Exam:
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Point tenderness of spine
Lower extremity weakness
Decreased rectal tone
Evaluation:
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Symptoms:
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STAT MRI Of Spine (all
levels)
Treatment:
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Start Dexamethasone 4-8
mg IV q 6h (as soon as
suspect)
Neurosurgery Consult
Radiation Oncology
consult
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Radiation is most
frequent treatment.
Oncologic Complications
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Malignant Pleural
Effusions
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Exudative
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Thoracentesis
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Send for cytology
Pleural biopsy
Caused by metastases 
to major lymphatic
structures or pleural
surface
Treatment:
Lymphatic/thoracic
duct obstruction
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Commonly caused by:
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Chylous
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Evaluation:
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Can be:
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Lung Cancer
Any other cancer with mets
to lung (Breast, Colon)
Non-Hodgkins lymphoma
(chylous)
Therapeutic thoracentesis
Chest-tube w/ talc
pleurodesis
Pleurex catheter
Oncologic Complications
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Pericardial Effusion
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Caused by local disease into
the pericardium or
hematogenous spread into
pericardium
Most frequent cancers:
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Peritoneal metastases
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Lung
Breast
Non-Hodgkins Lyphoma
If signs of tamponade on
echocardiogram, may
perform pericardial
window.
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Ovarian cancer
Colon cancer
Stomach cancer
Breast Cancer
Non-Hodgkins
Lymphoma
Diagnosis:
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Frequent cause of bowel
obstruction
Frequently seen in:
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Treatment:
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Ascites
Peritoneal carcinomatosis
Paracentesis – cytology
Treatment
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Symptomatic control
Breast Cancer
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Most common cause of cancer in females
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215,000 women diagnosed with and 40,000 died from breast cancer
in 2004.
Genetic Risk Factors:
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BRCA 1, BRCA 2
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Risk of breast cancer > 50% by age 60
Very high risk of ovarian cancer as well
Only present in ~ 5% of breast cancers
Only women who have very strong, premenopausal family history of
breast cancer should be tested for BRCA
90% reduction in breast cancer after prophylactic mastectomy
Oophorectomy may be ebeneficial
Number 1 risk factor for breast cancer is AGE!
Breast Cancer - Treatment
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Surgery
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Lumpectomy
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Mastectomy
Sentinel Node Mapping
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Injecting blue dye or radioactive material into tumor site/breast – if
sentinel node has no tumor, no further surgery needed.
If sentinel node positive, further axillary node biopsy needed
Estrogen Receptor (ER) positive? Progesterone Receptor (PR)
Positive?
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Frequently Breast Conserving therapy, with radiation
If yes – overall prognosis better, endocrine therapy useful (tamoxifen,
aromatase inhibitors)
Chemotherapy
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May include Herceptin (traztuzumab) if Her2-positive.
Colon cancer
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Age is greatest risk factor (90% of cases in patients > 50 years)
75% occur in patients without risk factors.
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Sign/Symptoms:
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Abdominal pain, bloating, constipation, diarrhea, hematochezia, melena
Iron deficiency anemia: Need to rule out colon cancer in anyone over age
50 presenting with iron-deficiency anemia!
Clinical features
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Remaining cases have family history, familial hereditary cancer syndromes,
inflammatory bowel disease.
Liver is most frequent site of metastases
Elevated CEA ( > 5 ng/mL) – higher value = worse prognosis
Treatment
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Surgery
Radiation
Chemotherapy – 5-Fluoruracil based regimens
Colon Cancer - Risk
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Familial Syndromes:
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Familial Adenomatous Polyposis (FAP)
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Autosomal Dominant, caused by mutations in the adenomatous
polyposis coli (APC) gene
Polyposis usually develops in the 2nd or 3rd decade of life (mean
age 16 years)
Diagnosis is made by presence of at least 100 polyps.
High risk for:
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Colon Cancer
Duodenal ampullary carcinoma
Follicular or papillary thyroid cancer
Childhood hepatoblastoma
Gastric carcinoma
CNS tumors (mostly medulloblastomas)
Familial Adenomatous Polyposis
Colon Cancer - Risk
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Familial Syndromes:
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Hereditary Non-Polyposis Colon Cancer (HNPCC)
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Autosomal dominant inheritance
Accounts for 2-3% of all colorectal adenocarcinomas
Characterized by: Early age of onset (mean age of 48 years), and
right side predominance of cancer
Can be:
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Lynch Syndrome Type I (Hereditary Site-Specific Colon Cancer):
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Characterized by malignant transformation of colorectal
adenomas.
Lynch Syndrome Type II (Cancer family syndrome):
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Has malignant transformation of colorectal adenomas.
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High risk of extracolonic tumors: Endometrial, ovarian,
stomach, small bowel, pancreas, hepatobiliary system, kidney,
prostate.
HNPCC
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Diagnosed via Amsterdam Criteria and/or Bethesda
Criteria:
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There should be at least three relatives with an HNPCCassociated cancer (colorectal cancer, cancer of the
endometrium, small bowel, ureter, or renal pelvis)
One should be a first degree relative of the other two
At least two successive generations should be affected
At least 1 should be diagnosed before age 50
Familial adenomatous polyposis should be excluded in the
colorectal cancer case(s) if any
Tumors should be verified by pathological examination
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Lung Cancer
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Number one cause of cancer death
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1 million new cases a year, and 900,000 deaths per year
Symptoms
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Asymptomatic “solitary pulmonary nodule”
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A lesion < 3cm seen on chest X-ray/chest CT
Malignant features include older age, tobacco use, irregular border, low
density on CT, doubling time < 1 year
If suspicion high, should biopsy
If suspicion low, should be monitored with subsequent studies
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3-4 months for first CT scan, 6 to 8 months for second, third scan at a
year
New or worsening Cough – most common symptom
Hoarse voice – left recurrent laryngeal nerve involvement
Hemoptysis
Lung Cancer – Small-Cell
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Small-Cell
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Central Location
Almost 100% smokers
Almost 100% metastases
Chemotherapy only, no surgery
Paraneoplastic syndromes:
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Eaton-Lambert Syndrome
SIADH
Ectopic ACTH
Lung Cancer – Non-Small Cell
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Squamous Cell
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Central Location
95% smokers
60% metastases
Paraneoplastic Syndrome:
Hypercalcemia
Large Cell
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Peripheral location
90% smokers
80% metastases
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Adenocarcinoma
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Peripheral location
50% smokers
80% metastases
Hypercoagulability
Hypertrophic pulmonary
osteoarthropathy
Lung Cancer
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Treatment:
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Surgery
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Chemotherapy
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Only way to cure lung cancer is to perform surgical excision of
Stage I
Works best in Small Cell Carcinoma (also the only option!)
Special Cases:
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Pancoast tumor
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Apical tumor
lower brachial plexopathy, shoulder pain, Horner’s syndrome
(unilateral constricted pupil, facial dryness, ptosis)
Prostate Cancer
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Incidence has doubled sinced PSA testing began.
The lifetime risk of developing prostate cancer is 17.8%
The lifetime risk of dying from prostate cancer is 3%.
Risk factors:
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Age (vast majority > 50 years of age)
African-American race
Diagnosis
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Gold standard – prostate biopsy
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Performed in patients with abnormal digital rectal exam or elevated serum PSA
Gleason score helps determine prognosis
PSA
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Some labs say abnormal if > 4 ng/mL; NOT diagnostic of cancer
Rate of change in PSA is most helpful.
Age specific
Most patients with metastatic prostate cancer have PSA well above 10
There are some patients with colon cancer with PSA < 4.
Prostate Cancer
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Treatment:
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Nothing
Prostatectomy
Radiation
Endocrine therapy
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Bilateral orchiectomy
GNRH-agonists
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Can cause impotence, hot flushes, gynecomastia, and loss of libido
Androgen-deprivation therapy
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Need to watch for osteopenia
Melanoma
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6th most common cause of cancer deaths.
Mean age of diagnosis is 53 years.
Risk Factors:
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Sun-sensitive skin type
Immunosuppression
Xeroderma pigmentosum
Family history of melanoma
Dysplastic mole syndrome
Multiple common or atypical nevi
Melanoma
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Types:
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Nodular melanoma
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15-30% of melanomas
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Most aggressive
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Can be amelanotic
Superficial Spreading
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Most common (70%)
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Often originates from previous dysplastic nevus
Acral Lentiginous Melanoma
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5% of melanomas
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Most common in dark-skinned individuals
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Usually occurs on hands, feet, nail beds
Lentigo maligna Melanoma
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5% of melanomas
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Usually occurs on Head, neck (sun-exposed areas)
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Can have long radial growth phase before vertical growth.
Melanoma
Superficial Spreading
Acral Lentiginous
Nodular
Lentigo maligna
Melanoma -Diagnosis
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A –Assymetry
B – Border
C – Color
D – Diameter (should not be more than 6 mm,
or pencil eraser)
E - Enlargement
Melanoma - Staging
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Clark’s – prognosis based on level of skin invaded
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Level I: Confined to epidermis (in situ); never metastasizes; 100% cure rate
Level II: Invasion into papillary dermis; invasion past basement membrane
(localized)
Level III: Tumor filling papillary dermis (localized), and compressing the
reticular dermis
Level IV: Invasion of reticular dermis (localized)
Level V: Invasion of subcutaneous tissue (regionalized by direct extension) S
Breslow’s – prognosis based on depth (in mm)
Stage I A: Lesion  1mm thick
 Stage I B: Lesion 1 –2 mm thick
 Stage II A: Lesion 2 – 4 mm thick
 Stage II B: Lesion > 4 mm thick.
*we use Breslow’s in real practice!
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Melanoma - Treatment
Question # 1
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A 59-year old man presents with cough,
dyspnea and facial edema of 2 weeks’
duration. He has a 40-pack year smoking
history. Except for an anteroseptal
myocardial infarction 4 years ago, he has been
healthy.
Question # 1 (cont.)
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Physical examination reveals a blood pressure of
130/85 mmHg and normal heart sounds with a pulse
rate of 72/min., but there is reduced air entry in the
right middle chest, dilated veins in the upper chest,
and a slightly tender liver palpable 3 cm below the
costal margin. The results of hematology and
chemistry screens (including liver function tests) are
normal, but a chest CT scan shows a central right
upper lobe mass, with collapse and extensive
mediastinal adenopathy. Blodd gases are within
normal limits, but spirometry shows an obstructive
pattern.
Question #1 (cont.)

The next step in management of this patient
would be:
(A)
(B)
(C)
(D)
(E)
Immediate radiotherapy
Immediate chemotherapy
Bronchoscopy
Mediastinoscopy
Intravenous furosemide
Question # 2
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A 36-year old woman with no previous
medical history presents with an eczematoid
scaly eruption on her left nipple. She says
that she has recently taken up jogging and this
has irritated her breast.
Question # 2 (cont.)
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On physical examination, she has a 1-cm reddened
and slighlty crusty lesion on the left nipple. There is
no discharge or masses or other abnormalities on
either breast. Topical skin treatment with emollients
and corticosteroids is prescribed, and she is told to
return for re-examination in 2 weeks. At return 2
weeks later, the crust is somewhat decreased, but the
scaly eruption on the nipple is still present, although
somewhat diminished. She has continued to jog.
Question # 2 (cont.)

Which of the following is the best course of
management?
(A)
(B)
(C)
(D)
(E)
Continue topical therapy
Continue topical therapy, and recommend she wear a
running bra or consider stopping her jogging program
Continue topical therapy, but add an antifungal agent
Order a mammogram, and refer her to a surgeon for
biopsy
Order a mammogram, and if negative, continue topical
therapy.
Question # 3
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A 70-year old male with advanced hormonerefractory prostate cancer presents with multifocal
pain, especially in hiss back. He has been treated by
bilateral orchiectomy and radiotherapy to the
hemipelvis. His PSA is 100 ng/mL, and a recent
bone scan showed multiple “hot spots”. He states
that he also has noticed increasing weakness of the
lower limbs and severe constipation despite the use
of stool softeners.
Question # 3 (cont.)
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The next step in management should be:
(A)
(B)
(C)
(D)
(E)
Cytotoxic chemotherapy
Referral for physical therapy
MRI of the spine
Increased laxatives
Referral for radioactive strontium