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Cancer – the Essentials. Michele Ritter, M.D. Argy Resident – February, 2007. 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

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Cancer the essentials l.jpg

Cancer – the Essentials

Michele Ritter, M.D.

Argy Resident – February, 2007


Risk factors fo cancer l.jpg

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

Risk Factors fo Cancer


Cancer prevention l.jpg
Cancer Prevention

  • Lung Cancer

    • Smoking cessation!!!

      • Tobacco is related to lung, head and neck, esophagus, pancreas, bladder, kidney, stomach and possibly ccolon and uterine cancers

      • Second hand smoke has been shown to be risk factor for lung cancer


Smoking cessation l.jpg
Smoking Cessation

  • The 5 “A’s” for smoking cessation

    • 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.

      • Includes counseling, pharmacotherapy, social support

    • Arrange: Schedule follow-up contact.


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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)


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    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


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    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 prevention8 l.jpg
    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


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    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.


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    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..


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    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.


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    Cancer Screening (cont.)

    • Colon Cancer

      • Beginning at age ≥ 50

      • Colonoscopy, flexible sigmoidoscopy, feocal 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 cont13 l.jpg
    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 l.jpg

    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


    Oncologic complications15 l.jpg

    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


    Oncologic complications16 l.jpg

    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


    Oncologic complications17 l.jpg

    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


    Oncologic complications18 l.jpg

    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

    Oncologic Complications


    Breast cancer l.jpg
    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 l.jpg
    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 l.jpg
    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


  • Lung cancer l.jpg
    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 l.jpg
    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 l.jpg

    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 – Non-Small Cell


    Lung cancer25 l.jpg
    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 l.jpg
    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 cancer27 l.jpg
    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


    Question 1 l.jpg
    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 l.jpg
    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 cont30 l.jpg
    Question #1 (cont.)

    • The next step in management of this patient would be:

      • Immediate radiotherapy

      • Immediate chemotherapy

      • Bronchoscopy

      • Mediastinoscopy

      • Intravenous furosemide


    Question 2 l.jpg
    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 l.jpg
    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 cont33 l.jpg
    Question # 2 (cont.)

    • Which of the following is the best course of management?

      • 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 l.jpg
    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 l.jpg
    Question # 3 (cont.)

    • The next step in management should be:

      • Cytotoxic chemotherapy

      • Referral for physical therapy

      • MRI of the spine

      • Increased laxatives

      • Referral for radioactive strontium