Cancer – the Essentials
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Transcript of Cancer – the Essentials
Cancer – the EssentialsMichele Ritter, M.D.
Argy Resident – February, 2007
Risk Factors for Cancer Breast
Early menarche, nulliparity, or late first full-term pregnancy
Exogenous estrogens Ionizing radiation Family History
Colon Family History Inflammatory Bowel Disease
Lung Tobacco Ionizing Radiation Asbestos (with tobacco)
Pleura/Mesothelioma Asbestos
Esophagus Tobacco Alcohol Barrett’s esophagus
Ovary Nulliparity
Pancreas Tobacco
Prostate Family history
Hepatocellular (liver) Hep. C, Hep. B Aflatoxin Vinyl chloride Alcohol (cirrhosis)
Urinary Bladder Tobacco Schistosoma haematobium Aromatic amine exposure
Cervical Human Papillomavirus
Endometrial Obesity Exogenous, unopposed estrogen Diabetes mellitus Low parity
Cancer Prevention Lung Cancer
Smoking cessation!!! 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 The 5 “A’s” for smoking cessation
1. Ask: Systematically identify all tobacco users at every visit
2. Advise: Strongly urge all tobacco users to quit3. Assess: Determine a patient’s willingness to
attempt to quit4. Assist: Aid the patient in quitting.
1. Includes counseling, pharmacotherapy, social support
5. Arrange: Schedule follow-up contact.
Smoking Cessation (cont.) Pharmacotherapy
Nicotine Replacement Design to ameliorate symptoms of nicotine withdrawal: anxiety, dysphoria
or depressive symptoms, insomnia, increased appetite/weight gain, Includes gum, patches, nasal spray, inhaler
Bupropion (Zyban) 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 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.) Breast Cancer
Tamoxifen therapy 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: Increased risk for endometrial cancer 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.) Colon Cancer
Possible benefit with NSAID use (specifically in patients with familial adenomatous polyposis) – but not yet recommended routinely.
Gastric Cancer Antibiotic eradiation of Helicobacter pylori -carotene, vitamin E, selenium supplementation
(in Chinese)
Cancer Prevention Prostate Cancer
Finasteride 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 Diet
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 Cervical Cancer
Pap Smear 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) HPV-DNA testing as follow-up if low-grade atypia or other
abnormalities found..
Cancer Screening (cont.) Breast Cancer
Mammogram Once every 1 to 2 years age 40-49 years Annual mammogram for age ≥ 50
Breast exam Either performed by patient or provider, has not been
found to have any effect on outcome.
Cancer Screening (cont.) Colon Cancer
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.) Prostate Cancer
USPSTF has not found evidence supporting the routine use of PSA. Also has not found that routine DRE is helpful.
Skin Cancer Routine screening for skin cancer using a total body skin exam not
recommended. Ovarian Cancer
Does not recommend vaginal ultrasound or CA-125 measurement Lung Cancer
No established guidelines yet for the use of screening CT of the chest
Oncologic Complications Hypercalcemia
The most common metabolic paraneoplastic syndrome
Seen in: Squamous cell carcinoma
(lung, head, neck) Frequently produce PTHrP
Multiple myeloma Breast carcinoma T-cell lymphoma Renal Cell carcinoma
Symptoms: Confusion Fatigue Constipation Nausea Polyuria
Management Vigorous hydration Lasix Bisphosphonates
Pamidronate Zoledronic acid
Oncologic Complications Superior Vena Cava
Syndrome Symptoms
Swelling face, neck, arms (especially when patient is supine)
Cough Dyspnea Hoarseness due to laryngeal edema Headaches (increased intracranial
pressure) Most commonly occurs in
Lung Cancer (small cell) Lymphoma (Hodgkin and non-
Hodgkin) Mediastinal germ cell tumors
Exam: Periorbital and arm
edema Elevated JVP Increased number of
collateral veins covering anterior chest wall
Diagnosed via: CT scan Should show right hilar
mass with SVC occlusion
An oncologic urgency Tissue diagnosis
recommended Radiation therapy (or
chemo. if small cell or lymphoma)
Oncologic Complications Spinal Cord Compression
Symptoms: New or significantly worsening
back pain/tenderness with neurologic deficits. Urinary incontinence, fecal
incontinence Lower extremity weakness
Exam: Point tenderness of spine Lower extremity weakness Decreased rectal tone
Evaluation: STAT MRI Of Spine (all
levels) Treatment:
Start Dexamethasone 4-8 mg IV q 6h (as soon as suspect)
Neurosurgery Consult Radiation Oncology
consult Radiation is most
frequent treatment.
Oncologic Complications Malignant Pleural
Effusions Can be:
Exudative Caused by metastases
to major lymphatic structures or pleural surface
Chylous Lymphatic/thoracic
duct obstruction Commonly caused by:
Lung Cancer Any other cancer with mets
to lung (Breast, Colon) Non-Hodgkins lymphoma
(chylous)
Evaluation: Thoracentesis
Send for cytology Pleural biopsy
Treatment: Therapeutic thoracentesis Chest-tube w/ talc
pleurodesis Pleurex catheter
Oncologic Complications Pericardial Effusion
Caused by local disease into the pericardium or hematogenous spread into pericardium
Most frequent cancers: Lung Breast Non-Hodgkins Lyphoma
Treatment: If signs of tamponade on
echocardiogram, may perform pericardial window.
Peritoneal metastases Ascites Peritoneal carcinomatosis
Frequent cause of bowel obstruction
Frequently seen in: Ovarian cancer Colon cancer Stomach cancer Breast Cancer Non-Hodgkins
Lymphoma Diagnosis:
Paracentesis – cytology Treatment
Symptomatic control
Breast Cancer Most common cause of cancer in females
215,000 women diagnosed with and 40,000 died from breast cancer in 2004.
Genetic Risk Factors: BRCA 1, BRCA 2
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 Surgery
Lumpectomy Frequently Breast Conserving therapy, with radiation
Mastectomy Sentinel Node Mapping
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? If yes – overall prognosis better, endocrine therapy useful (tamoxifen,
aromatase inhibitors) Chemotherapy
May include Herceptin (traztuzumab) if Her2-positive.
Colon cancer Age is greatest risk factor (90% of cases in patients > 50 years) 75% occur in patients without risk factors.
Remaining cases have family history, familial hereditary cancer syndromes, inflammatory bowel disease.
Sign/Symptoms: 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
Liver is most frequent site of metastases Elevated CEA ( > 5 ng/mL) – higher value = worse prognosis
Treatment Surgery Radiation Chemotherapy – 5-Fluoruracil based regimens
Colon Cancer - Risk Familial Syndromes:
Familial Adenomatous Polyposis (FAP) 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:
Colon Cancer Duodenal ampullary carcinoma Follicular or papillary thyroid cancer Childhood hepatoblastoma Gastric carcinoma CNS tumors (mostly medulloblastomas)
Familial Adenomatous Polyposis
Colon Cancer - Risk Familial Syndromes:
Hereditary Non-Polyposis Colon Cancer (HNPCC) 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:
Lynch Syndrome Type I (Hereditary Site-Specific Colon Cancer): Characterized by malignant transformation of colorectal
adenomas. Lynch Syndrome Type II (Cancer family syndrome):
Has malignant transformation of colorectal adenomas. High risk of extracolonic tumors: Endometrial, ovarian, stomach,
small bowel, pancreas, hepatobiliary system, kidney, prostate.
HNPCC Diagnosed via Amsterdam Criteria and/or Bethesda
Criteria: There should be at least three relatives with an HNPCC-
associated 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
Lung Cancer Number one cause of cancer death
1 million new cases a year, and 900,000 deaths per year Symptoms
Asymptomatic “solitary pulmonary nodule” 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
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 Small-Cell
Central Location Almost 100% smokers Almost 100% metastases Chemotherapy only, no surgery Paraneoplastic syndromes:
Eaton-Lambert Syndrome SIADH Ectopic ACTH
Lung Cancer – Non-Small Cell Squamous Cell
Central Location 95% smokers 60% metastases Paraneoplastic Syndrome:
Hypercalcemia
Large Cell Peripheral location 90% smokers 80% metastases
Adenocarcinoma Peripheral location 50% smokers 80% metastases Hypercoagulability Hypertrophic pulmonary
osteoarthropathy
Lung Cancer Treatment:
Surgery Only way to cure lung cancer is to perform surgical excision of
Stage I
Chemotherapy Works best in Small Cell Carcinoma (also the only option!)
Special Cases: Pancoast tumor
Apical tumor lower brachial plexopathy, shoulder pain, Horner’s syndrome
(unilateral constricted pupil, facial dryness, ptosis)
Prostate Cancer 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:
Age (vast majority > 50 years of age) African-American race
Diagnosis Gold standard – prostate biopsy
Performed in patients with abnormal digital rectal exam or elevated serum PSA Gleason score helps determine prognosis
PSA 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 Treatment:
Nothing Prostatectomy Radiation Endocrine therapy
Bilateral orchiectomy GNRH-agonists
Can cause impotence, hot flushes, gynecomastia, and loss of libido Androgen-deprivation therapy
Need to watch for osteopenia
Melanoma 6th most common cause of cancer deaths. Mean age of diagnosis is 53 years. Risk Factors:
Sun-sensitive skin type Immunosuppression Xeroderma pigmentosum Family history of melanoma Dysplastic mole syndrome Multiple common or atypical nevi
Melanoma Types:
Nodular melanoma 15-30% of melanomas Most aggressive Can be amelanotic
Superficial Spreading Most common (70%) Often originates from previous dysplastic nevus
Acral Lentiginous Melanoma 5% of melanomas Most common in dark-skinned individuals Usually occurs on hands, feet, nail beds
Lentigo maligna Melanoma 5% of melanomas Usually occurs on Head, neck (sun-exposed areas) Can have long radial growth phase before vertical growth.
Melanoma
Superficial SpreadingNodular
Acral Lentiginous Lentigo maligna
Melanoma -Diagnosis A –Assymetry B – Border C – Color D – Diameter (should not be more than 6 mm,
or pencil eraser) E - Enlargement
Melanoma - Staging Clark’s – prognosis based on level of skin invaded
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!
Melanoma - Treatment
Question # 1 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.) 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) Immediate radiotherapy
(B) Immediate chemotherapy
(C) Bronchoscopy
(D) Mediastinoscopy
(E) Intravenous furosemide
Question # 2 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.) 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) Continue topical therapy
(B) Continue topical therapy, and recommend she wear a running bra or consider stopping her jogging program
(C) Continue topical therapy, but add an antifungal agent
(D) Order a mammogram, and refer her to a surgeon for biopsy
(E) Order a mammogram, and if negative, continue topical therapy.
Question # 3 A 70-year old male with advanced hormone-
refractory 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.) The next step in management should be:
(A) Cytotoxic chemotherapy
(B) Referral for physical therapy
(C) MRI of the spine
(D) Increased laxatives
(E) Referral for radioactive strontium