1

CANCER DATACANCER DATA

2

Gynecological Cancer

Five main types of cancer affect a woman's Five main types of cancer affect a woman's reproductive organs: reproductive organs:

1.1. cervical, 11,999 / 3,924cervical, 11,999 / 3,924

2.2. ovarian, 19,842 / 14,787ovarian, 19,842 / 14,787

3.3. uterine, 37,465 uterine, 37,465

4.4. Vaginal*, and Vaginal*, and

5.5. Vulvar*. Vulvar*.

*very rare*very rare

In 2005, 75,144 women In 2005, 75,144 women were told that they had were told that they had a gynecologic cancer, a gynecologic cancer, and 27,259 died from a and 27,259 died from a gynecologic cancer.gynecologic cancer.

3

SOME STATS

2nd most common cause of death in the U.S.2nd most common cause of death in the U.S.1.4million new cases/559,000 deaths (2007)1.4million new cases/559,000 deaths (2007)Lifetime probability of developing cancer is: Lifetime probability of developing cancer is:

46% for men, 38% for women.46% for men, 38% for women.Breast cancer- 1 in 7 women.Breast cancer- 1 in 7 women.Prostate cancer- 1 in 6 men.Prostate cancer- 1 in 6 men.55% of all new cancers and over 50% of cancer deaths – 55% of all new cancers and over 50% of cancer deaths – lung, prostate, breast, colon/rectum.lung, prostate, breast, colon/rectum.Leading cause of cancer death in the U.S. is lung.Leading cause of cancer death in the U.S. is lung.

4

Human carcinogens - environmental

AflatoxinsAflatoxins AsbestosAsbestos BenzeneBenzene CadmiumCadmium Coal tarCoal tar

CreosoteCreosoteDDTDDTPolycyclic aromatic Polycyclic aromatic hydrocarbonshydrocarbonsRadonRadonSolar radiationSolar radiation

5

Physical Carcinogens

Ultraviolet lightUltraviolet light Ionizing radiation (X-rays)Ionizing radiation (X-rays) AsbestosAsbestos XenobioticsXenobiotics

6

7

XENOBIOTICS

Chemical substances that are foreign to the biological Chemical substances that are foreign to the biological system. They include naturally occurring compounds, system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticide, drugs, environmental agents, carcinogens, insecticide, etcetc

8

Viral Carcinogenesis

Viral infections account for an Viral infections account for an estimated one in seven estimated one in seven human cancers worldwidehuman cancers worldwideMajority of these are due to infection with two DNA Majority of these are due to infection with two DNA virusesvirusesHBV - linked to hepatocellular HBV - linked to hepatocellular carcinomacarcinomaHPV - linked to cervical HPV - linked to cervical carcinomacarcinoma

9

EBV - Involvement in Human TumorsAfrican Burkitt lymphomaAfrican Burkitt lymphomaB-cell lymphomas of immunosuppressed patientsB-cell lymphomas of immunosuppressed patientsSome cases of Hodgkin lymphomaSome cases of Hodgkin lymphomaNasopharyngeal carcinomasNasopharyngeal carcinomas

10

How Do Viruses like HPV and HBV Cause Cancer?Very small virusesVery small viruses

Can integrate their viral DNA into host genomeCan integrate their viral DNA into host genome

They code for viral proteins which block tumor They code for viral proteins which block tumor suppressor suppressor

proteins in cellsproteins in cells

11

Oncogenic Viruses

Human papillomaviruses - HPVHuman papillomaviruses - HPV Epstein-Barr Virus (EBV)Epstein-Barr Virus (EBV) Human herpesvirus 8 (HHV8)Human herpesvirus 8 (HHV8) Hepatitis B virus - HBVHepatitis B virus - HBV Hepatitis C virus - HCVHepatitis C virus - HCV HTLV-I, HTLV-IIHTLV-I, HTLV-II

12

Helicobacter pylori

Gastric infection linked to gastric lymphomas and Gastric infection linked to gastric lymphomas and adenocarcinomasadenocarcinomasDetection of H pylori in majority of Detection of H pylori in majority of cases of gastric cases of gastric lymphomaslymphomasAntibiotic treatment results in gastric lymphoma regression in Antibiotic treatment results in gastric lymphoma regression in

most casesmost cases

13

HOW CAN A PATIENT ACQUIRE ONE OF THESE MUTATIONS?

1) Inheritance.1) Inheritance.2) A spontaneous mutation.2) A spontaneous mutation.3) A mutation induced by environmental exposure, infective agents,3) A mutation induced by environmental exposure, infective agents,

“ “other factors.”other factors.”4) A mutation occurring as a result of accelerated cellular division. 4) A mutation occurring as a result of accelerated cellular division.

14

BRCA 1 and 2 Families with a history of multiple cases of breast cancer, cases of both breast and Families with a history of multiple cases of breast cancer, cases of both breast and

ovarian cancer, one or more family members with two primary cancers (original ovarian cancer, one or more family members with two primary cancers (original tumors at different sites), or an Ashkenazi (Eastern European) Jewish background.tumors at different sites), or an Ashkenazi (Eastern European) Jewish background.

Increases risk of developing these cancers at a young age Increases risk of developing these cancers at a young age Breast:(Breast:(36 to 85 percent36 to 85 percent (360-850 out of 1,000) of women with an altered (360-850 out of 1,000) of women with an altered

BRCA1 or BRCA2 gene) (13.2 percent (132 out of 1,000 individuals) BRCA1 or BRCA2 gene) (13.2 percent (132 out of 1,000 individuals) Ovarian:Ovarian: 16 to 60 percent16 to 60 percent (160-600 out of 1,000) of women with altered BRCA1 (160-600 out of 1,000) of women with altered BRCA1

or BRCA2 genes 1.7 percent (17 out of 1,000)or BRCA2 genes 1.7 percent (17 out of 1,000)

15

SOME EXAMPLES

PRIOR CHEMO OR RADIATIONPRIOR CHEMO OR RADIATION

Associated with the development of a subsequent malignancy, especially Associated with the development of a subsequent malignancy, especially leukemia and solid tumors.leukemia and solid tumors.

16

ESTROGEN & PROGESTERONE

Combined estrogen & progesterone confers a markedly increased risk of Combined estrogen & progesterone confers a markedly increased risk of developing breast cancer.developing breast cancer.

The Women’s Health Initiative (WHI)- showed an increased risk of breast The Women’s Health Initiative (WHI)- showed an increased risk of breast cancer, as well as heart disease, stroke, and blood clots, but a decreased cancer, as well as heart disease, stroke, and blood clots, but a decreased risk of colon cancer and hip fractures.risk of colon cancer and hip fractures.

The study was stopped early when the risk was found to be greater than the The study was stopped early when the risk was found to be greater than the benefit.benefit.

17

CANCER PREVENTION

PRIMARY PREVENTIONPRIMARY PREVENTION SECONDARY PREVENTIONSECONDARY PREVENTION

18

PRIMARY PREVENTION

1) LIFESTYLE MODIFICATION1) LIFESTYLE MODIFICATIONa) SMOKING.a) SMOKING.b) DIET / OBESITY.b) DIET / OBESITY.c) OTHER.c) OTHER.

2) CHEMOPREVENTION2) CHEMOPREVENTIONa) RETINOIDS.a) RETINOIDS.b) ASPIRIN, NSAID’s.b) ASPIRIN, NSAID’s.c) BETA CAROTENE, VITAMIN E.c) BETA CAROTENE, VITAMIN E.d) CALCIUM, SELENIUM.d) CALCIUM, SELENIUM.e) TAMOXIFEN, RALOXIFENE.e) TAMOXIFEN, RALOXIFENE.f) ISOFLAVONES, FINASTERIDE.f) ISOFLAVONES, FINASTERIDE.

19

LIFESTYLE MODIFICATION

SMOKINGSMOKING Linked to cancers of the: lung, head & neck, esophagus, pancreas, kidney, Linked to cancers of the: lung, head & neck, esophagus, pancreas, kidney,

and bladder, and a 30% increase in the risk of death from colon cancer, and and bladder, and a 30% increase in the risk of death from colon cancer, and a higher mortality in breast cancer.a higher mortality in breast cancer.

Associated w/ # of years and # of packs smoked per day, the “pack-year.”Associated w/ # of years and # of packs smoked per day, the “pack-year.” Risk decreases every year after quitting, but may not approach that of those Risk decreases every year after quitting, but may not approach that of those

who never smoked.who never smoked.

20

LIFESTYLE MODIFICATION

DIET – FATS OR FRUITS?DIET – FATS OR FRUITS? The data can be confusing, and please read them yourself, but it appears we should The data can be confusing, and please read them yourself, but it appears we should

be telling our patients to consume less fat, especially saturated/animal fat, and more be telling our patients to consume less fat, especially saturated/animal fat, and more fruits and veggies.fruits and veggies.

There may be confounding variables, ie persons w/ a diet high in fat tend to also be There may be confounding variables, ie persons w/ a diet high in fat tend to also be obese, and it may be the obesity or other elements in the obese patient, rather than obese, and it may be the obesity or other elements in the obese patient, rather than the actual fat, that is associated with the increased risk of cancer.the actual fat, that is associated with the increased risk of cancer.

21

LIFESTYLE MODIFICATION

DIET – FIBERDIET – FIBER Fiber is good, especially for things like smooth glycemic control and Fiber is good, especially for things like smooth glycemic control and

prevention of diverticular disease, but the data do not show that a high-prevention of diverticular disease, but the data do not show that a high-fiber diet decreases the risk of colorectal cancer.fiber diet decreases the risk of colorectal cancer.

22

LIFESTYLE MODIFICATIONDIET – PHYTOESTROGENSDIET – PHYTOESTROGENS

Plant-derived substances such as isoflavones, lignans, and coumestans that have Plant-derived substances such as isoflavones, lignans, and coumestans that have weak estrogenic effects.weak estrogenic effects.

Dietary data re phytoestrogens hindered by issues inherent in a recall-type study, Dietary data re phytoestrogens hindered by issues inherent in a recall-type study, but a reduced incidence of breast cancer is seen in women in places such as Asia but a reduced incidence of breast cancer is seen in women in places such as Asia where diets are high in phytoestrogens.where diets are high in phytoestrogens.

Data re phytoestrogen supplements still being collected. There are no data to Data re phytoestrogen supplements still being collected. There are no data to suggest that phytoestrogen supplements increase the risk of breast cancer.suggest that phytoestrogen supplements increase the risk of breast cancer.

23

LIFESTYLE MODIFICATIONDIET –OBESITYDIET –OBESITY

A risk factor for cancers of the:A risk factor for cancers of the: Breast, colon & rectum, and lung, Breast, colon & rectum, and lung,

even in non-smokers.even in non-smokers. Increased BMI* and hypertension Increased BMI* and hypertension

associated w/ increased risk of associated w/ increased risk of renal cell carcinoma in men.renal cell carcinoma in men.

*BMI= body mass index*BMI= body mass index kg/m2 kg/m2 http://apps.usa.gov/bmi-app/http://apps.usa.gov/bmi-app/ 2007 Survey: 63% of 2007 Survey: 63% of

Americans are overweight, with Americans are overweight, with 26% now in the obese category 26% now in the obese category (a BMI of 30 or more) (a BMI of 30 or more)

Category BMI range – kg/m2

Emaciation less than 16.0

Underweight from 16.0 to 18.5

Normal from 18.5 to 25

Overweight from 25 to 30

Obese Class IObese Class I from 30 to 35from 30 to 35

Obese Class IIObese Class II from 35 to 40from 35 to 40

Obese Class IIIObese Class III Over 40Over 40

24

LIFESTYLE MODIFICATIONOTHEROTHER

Breast feeding for at least 1 year w/ 1 or more pregnancies is associated w/ Breast feeding for at least 1 year w/ 1 or more pregnancies is associated w/ a reduced risk of breast cancer.a reduced risk of breast cancer.

Korean women who breast feed for less than a year had a 20% lower risk Korean women who breast feed for less than a year had a 20% lower risk of breast cancer, 40% if more than 2 years, compared to women who’ve of breast cancer, 40% if more than 2 years, compared to women who’ve never breast fed.never breast fed.

In 1 study, 2 or more glasses of wine per day was associated with a 50% In 1 study, 2 or more glasses of wine per day was associated with a 50% increase in breast cancer.increase in breast cancer.

25

CHEMOPREVENTION

RETINOIDSRETINOIDS Retinoids are modulators of epithelial cell differentiation, regulating Retinoids are modulators of epithelial cell differentiation, regulating

cellular growth and differentiation and apoptosis.cellular growth and differentiation and apoptosis. Isotretinoin has been shown to suppress leukoplakia, a premalignant Isotretinoin has been shown to suppress leukoplakia, a premalignant

squamous cell lesion in the “aerodigestive tract.”squamous cell lesion in the “aerodigestive tract.” Also looked at in the prevention of second primaries in patients with early Also looked at in the prevention of second primaries in patients with early

malignancies of the head & neck. See text for details.malignancies of the head & neck. See text for details.

26

CHEMOPREVENTION

““Prevention of cancer by administering chemical compounds that interfere with Prevention of cancer by administering chemical compounds that interfere with the multi staged carcinogenic process.”the multi staged carcinogenic process.”

Interventions aimed at:Interventions aimed at: 1) Patients with a Dx of malignancy- to prevent a second.1) Patients with a Dx of malignancy- to prevent a second. 2) Patients with a premalignant lesion (dysplasia).2) Patients with a premalignant lesion (dysplasia). 3) Patients at high risk (family Hx).3) Patients at high risk (family Hx). 4) The general population.4) The general population. Need to be safe and well-tolerated.Need to be safe and well-tolerated.

27

CHEMOPREVENTION

ASPIRIN, NSAID’sASPIRIN, NSAID’s In short, regular aspirin use (16 or more 325 mg doses per month for at least 1 year) In short, regular aspirin use (16 or more 325 mg doses per month for at least 1 year)

is associated with a reduced risk of fatal colon cancer by as much as 40-50%.is associated with a reduced risk of fatal colon cancer by as much as 40-50%. Aspirin may also protect against cancers of the esophagus, stomach, and rectum.Aspirin may also protect against cancers of the esophagus, stomach, and rectum.

28

CHEMOPREVENTION

BETA-CAROTENE & VITAMIN BETA-CAROTENE & VITAMIN E ?E ? Function as anti-oxidants.Function as anti-oxidants. Studies do not support the role of supplementation with beta-carotene as a Studies do not support the role of supplementation with beta-carotene as a

means of reducing cancer risk.means of reducing cancer risk. In fact, a couple of studies found a much higher rate (28%) of cancer in the In fact, a couple of studies found a much higher rate (28%) of cancer in the

supplement group, as well as mortality from all causes (17%) and supplement group, as well as mortality from all causes (17%) and cardiovascular disease(26%).cardiovascular disease(26%).

Vitamin E may show more positive results, but data are still being gathered.Vitamin E may show more positive results, but data are still being gathered.

29

CHEMOPREVENTION

CALCIUM AND SELENIUMCALCIUM AND SELENIUM On-going data collection via the “SELECT” study.On-going data collection via the “SELECT” study. Calcium is felt to lower colon cancer risk by binding bile salts and Calcium is felt to lower colon cancer risk by binding bile salts and

reducing bile-induced mucosal damage.reducing bile-induced mucosal damage. Selenium is already felt to reduce prostate and skin cancer risk.Selenium is already felt to reduce prostate and skin cancer risk.

30

CHEMOPREVENTION

TAMOXIFENTAMOXIFEN A “SERM” – selective estrogen receptor modulator. Depending on the A “SERM” – selective estrogen receptor modulator. Depending on the

receptor, it has either estrogenic activity (uterus) or anti-estrogenic activity receptor, it has either estrogenic activity (uterus) or anti-estrogenic activity (breast).(breast).

Its use is well established in reducing the risk of developing a second Its use is well established in reducing the risk of developing a second primary in the opposite breast in women with a diagnosis of breast cancer. primary in the opposite breast in women with a diagnosis of breast cancer. A form of adjuvant therapy.A form of adjuvant therapy.

Works only for breast cancers that are estrogen receptor positive.Works only for breast cancers that are estrogen receptor positive.

31

CHEMOPREVENTION

FINASTERIDEFINASTERIDE See text. See text. A 5-alpha reductase inhibitor, prevents the conversion of testosterone to A 5-alpha reductase inhibitor, prevents the conversion of testosterone to

dihydro-testosterone.dihydro-testosterone. Reduces the risk of developing prostate cancer by 25%,Reduces the risk of developing prostate cancer by 25%,

32

SECONDARY PREVENTION Early detection by screening asymptomatic patients.Early detection by screening asymptomatic patients. Shown to be effective at reducing mortality for cancers of the:Shown to be effective at reducing mortality for cancers of the: 1) Breast.1) Breast. 2) Colon.2) Colon. 3) Cervix.3) Cervix. 4) Prostate.4) Prostate. 5) Oral cavity.5) Oral cavity. 6) Skin.6) Skin.

33

STAGING OF MALIGNANCY Useful for:Useful for: 1) Prognosis.1) Prognosis. 2) Treatment.2) Treatment. 3) Uniformity for purposes of comparing mortality rates, outcome of 3) Uniformity for purposes of comparing mortality rates, outcome of

treatment, etc.treatment, etc. TNM Classification:TNM Classification: T describes the size of the tumor and whether it has invaded nearby tissue,T describes the size of the tumor and whether it has invaded nearby tissue, N describes regional lymph nodes that are involved,N describes regional lymph nodes that are involved, M describes distant metastasis (spread of cancer from one body part to M describes distant metastasis (spread of cancer from one body part to

another).another).

34

TREATMENT

SURGERY.SURGERY. RADIATION.RADIATION. SYSTEMIC THERAPY.SYSTEMIC THERAPY. ADJUVANT THERAPY.ADJUVANT THERAPY.

35

TREATMENT

SURGERYSURGERY Useful for diagnosis, staging, and treatment.Useful for diagnosis, staging, and treatment. Potentially curable for early-stage lesions.Potentially curable for early-stage lesions. Not all tumors are surgically resectable (spinal cord, brain stem), may be too Not all tumors are surgically resectable (spinal cord, brain stem), may be too

diffuse/multi-focal (Hodgkins, leukemia, or may be disfiguring, as for breast diffuse/multi-focal (Hodgkins, leukemia, or may be disfiguring, as for breast cancer, osteosaracoma.)cancer, osteosaracoma.)

For these patients, some form of combined surgery-chemo-radiation or even For these patients, some form of combined surgery-chemo-radiation or even chemo and/or radiation may be possible.chemo and/or radiation may be possible.

36

TREATMENT

RADIATIONRADIATION More than 50% of all patients with cancer receive radiation at some point.More than 50% of all patients with cancer receive radiation at some point. Can be curative while allowing for organ conservation, such as carcinoma Can be curative while allowing for organ conservation, such as carcinoma

of the larynx.of the larynx. Has the potential for radiation-induced side-effects/burns – skin, radiation Has the potential for radiation-induced side-effects/burns – skin, radiation

proctitis, etc.proctitis, etc.

37

SYSTEMIC THERAPY USES:USES: 1) For cure.1) For cure. 2) Adjuvant therapy- to decrease the rate of relapse or improve the disease-free 2) Adjuvant therapy- to decrease the rate of relapse or improve the disease-free

interval.interval. 3) For palliation and prolonging the survival in patients with incurable 3) For palliation and prolonging the survival in patients with incurable

malignancies.malignancies. 4) Preoperative or “neoadjuvant” therapy- to reduce the size and extent of a 4) Preoperative or “neoadjuvant” therapy- to reduce the size and extent of a

primary tumor, making it more amenable to surgical removal with less local primary tumor, making it more amenable to surgical removal with less local destruction, even allowing for breast/organ-sparing surgery.destruction, even allowing for breast/organ-sparing surgery.

38

SYSTEMIC THERAPY

TYPES:TYPES: 1) Cytotoxic drugs (chemotherapy).1) Cytotoxic drugs (chemotherapy). 2) Hormones.2) Hormones. 3) Hormone antagonists. 3) Hormone antagonists. 4) Other agents.4) Other agents.

39

CYTOTOXIC DRUGS

Curative for: Hodgkin’s Disease, lymphomas, carcinoma of the testis, Curative for: Hodgkin’s Disease, lymphomas, carcinoma of the testis, some leukemias, and embryonal cell carcinoma.some leukemias, and embryonal cell carcinoma.

Combined with surgery and sometime irradiation, can increase the long-Combined with surgery and sometime irradiation, can increase the long-term control and cure of: breast cancer, cervical cancer, some lung cancers, term control and cure of: breast cancer, cervical cancer, some lung cancers, cancers of the colon and rectum, esophagus, stomach, and osteogenic cancers of the colon and rectum, esophagus, stomach, and osteogenic sarcoma.sarcoma.

40

HORMONAL THERAPY

BISPHOSPHANATESBISPHOSPHANATES-- Inhibit osteoclast activation.Inhibit osteoclast activation. Useful in reducing bone pain in patients with skeletal metastases.Useful in reducing bone pain in patients with skeletal metastases. Also being studied and used to reduce the frequency of skeletal metastases.Also being studied and used to reduce the frequency of skeletal metastases.

41

ADJUVANT CHEMOTHERAPY

To eradicate or suppress minimal residual disease after surgery or To eradicate or suppress minimal residual disease after surgery or irradiation (“micrometastases”).irradiation (“micrometastases”).

Effective in cancers of the breast, colon, stomach, esophagus, bladder, Effective in cancers of the breast, colon, stomach, esophagus, bladder, prostate, ovary, osteogenic sarcoma, malignant melanoma.prostate, ovary, osteogenic sarcoma, malignant melanoma.

Tumor recurrence after adjuvant chemotherapy usually signifies Tumor recurrence after adjuvant chemotherapy usually signifies

incurabilityincurability..

42

TOXICITY OF CHEMOTHERAPY

BONE MARROW SUPPRESSION.BONE MARROW SUPPRESSION. NAUSEA & VOMITING.NAUSEA & VOMITING. G.I., SKIN.G.I., SKIN. MISCELLANEOUS. MISCELLANEOUS.

43

TOXICITY OF CHEMOTHERAPY

BONE MARROW SUPPRESSIONBONE MARROW SUPPRESSION The most serious and limiting toxicity.The most serious and limiting toxicity. Treated with:Treated with: 1) Bone marrow transplant for high dose chemo.1) Bone marrow transplant for high dose chemo. 2) Myeloid growth factors to combat leukopenia, erythrocytopenia, and 2) Myeloid growth factors to combat leukopenia, erythrocytopenia, and

thrombocytopenia in standard dose chemo.thrombocytopenia in standard dose chemo.

44

TOXICITY OF CHEMOTHERAPY

NAUSEA & VOMITINGNAUSEA & VOMITING Common. CTZ actvityCommon. CTZ actvity A variety of antiemetics.A variety of antiemetics.

45

EVALUATION OF TUMOR RESPONSE 1) TUMOR SIZE.1) TUMOR SIZE. 2) TUMOR MARKERS.2) TUMOR MARKERS.

46

EVALUATION OF TUMOR RESPONSE

TUMOR SIZETUMOR SIZE

Assessed by a variety of methods, most of which involve some sort of Assessed by a variety of methods, most of which involve some sort of imaging technique- X-Ray, CT, MRI, ultrasound, gallium scan, PET scan, imaging technique- X-Ray, CT, MRI, ultrasound, gallium scan, PET scan, etc.etc.

47

EVALUATION OF TUMOR RESPONSE

TUMOR MARKERSTUMOR MARKERS

EXAMPLES:EXAMPLES:

HCG-HCG- in choriocarcinoma and testicular cancer. in choriocarcinoma and testicular cancer. PSA-PSA- in prostate cancer. in prostate cancer. IMMUNOGLOBULINS-IMMUNOGLOBULINS- in multiple meyloma. in multiple meyloma. STEROIDS-STEROIDS- in paraneoplastic Cushing’s. in paraneoplastic Cushing’s. Can measure the protein or its metabolite(s).Can measure the protein or its metabolite(s).

48

EVALUATION OF TUMOR RESPONSE

TUMOR MARKERSTUMOR MARKERS

EXAMPLES OF FETAL ANTIGENS:EXAMPLES OF FETAL ANTIGENS:

AFP-AFP- alpha-fetoprotein- in hepatocellular carcinoma, testicular cancer, alpha-fetoprotein- in hepatocellular carcinoma, testicular cancer, teratoembryonal carcinoma, gastric cancer.teratoembryonal carcinoma, gastric cancer.

CA 125-CA 125- in ovarian cancer. in ovarian cancer. CEA-CEA- carcinoembryonic antigen- in cancers of the colon, lung, breast, pancreas. carcinoembryonic antigen- in cancers of the colon, lung, breast, pancreas.

49

PARANEOPLASTIC SYNDROMES From production by the tumor cells of proteins/hormones, the genes for From production by the tumor cells of proteins/hormones, the genes for

which are generally suppressed in mature, differentiated cells.which are generally suppressed in mature, differentiated cells. EXAMPLES:EXAMPLES: ACTH, PTH, ADH. ACTH, PTH, ADH. These syndromes may be the 1These syndromes may be the 1stst indication of an underlying malignancy, indication of an underlying malignancy,

present in up to 15% of patients w/ cancer.present in up to 15% of patients w/ cancer. May be a more urgent hazard to life than the cancer.May be a more urgent hazard to life than the cancer.

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GENETIC DISORDERSGENETIC DISORDERSDownsDownsHomocysteineHomocysteineKlinefelterKlinefelterMarfanMarfanTurnerTurner

51

REVIEW

PATTERNS OF INHERITANCEPATTERNS OF INHERITANCE Single gene / Mendelian inheritance-autosomal dominant and recessive, X-Single gene / Mendelian inheritance-autosomal dominant and recessive, X-

linked.linked. Multifactorial.Multifactorial. Chromosomal- translocation, insertion, deletion, non-disjunction.Chromosomal- translocation, insertion, deletion, non-disjunction. Phenotype, genotype.Phenotype, genotype. Heterozygous, homozygous.Heterozygous, homozygous.

52

DOWN SYNDROME

From non-disjunction of chromosome #21, but can be due to an unbalanced From non-disjunction of chromosome #21, but can be due to an unbalanced translocation from a parent with a balanced translocation.translocation from a parent with a balanced translocation.

Incidence rises with increasing maternal Incidence rises with increasing maternal age.age. Risk at age 40 = 1/40.Risk at age 40 = 1/40. Characteristic phenotype.Characteristic phenotype. Antenatal screening: AFP; AFP + HCG + ESTRIOL; Nuchal skin fold Antenatal screening: AFP; AFP + HCG + ESTRIOL; Nuchal skin fold

thickness on sono.thickness on sono. Dx: by amniocentesis and karyotypeDx: by amniocentesis and karyotype..

53

HOMOCYSTEINURIA

A deficiency of cystathionine A deficiency of cystathionine ββ-synthase, an enzyme involved in the -synthase, an enzyme involved in the metabolism of homocysteine (from methionine).metabolism of homocysteine (from methionine).

Inheritance: autosomal recessive.Inheritance: autosomal recessive. Results in accumulation of homocysteine.Results in accumulation of homocysteine. Body habitus similar to Marfan’s, ectopia lentis, mental retardation, Body habitus similar to Marfan’s, ectopia lentis, mental retardation,

hypercoagulability.hypercoagulability.

54

MARFAN’S SYNDROME

Autosomal dominant.Autosomal dominant. A systemic connective tissue disorder.A systemic connective tissue disorder. Tall, arachnodactyly, ectopia lentis (similar to homocysteinuria).Tall, arachnodactyly, ectopia lentis (similar to homocysteinuria). Pectus excavatum, joint dislocations.Pectus excavatum, joint dislocations. Cardiac- mitral v. prolapse w/ regurg, chordae tendonae rupture.Cardiac- mitral v. prolapse w/ regurg, chordae tendonae rupture. Aorta- dissecting aortic aneurysm w/ rupture.Aorta- dissecting aortic aneurysm w/ rupture. See text for Dx criteria.See text for Dx criteria.

55

Marfan’s

56

TURNERS SYNDROME- XO1 out of every 2,500 female live births worldwide.1 out of every 2,500 female live births worldwide.Short neck with a webbed appearance Short neck with a webbed appearance A low hairline at the back of the neck, and low-set ears. A low hairline at the back of the neck, and low-set ears. Hands and feet of affected individuals may be swollen or puffy at birth, Hands and feet of affected individuals may be swollen or puffy at birth, have soft nails that turn upward at the ends when they are older.have soft nails that turn upward at the ends when they are older.Due to developmental due to obstruction of the lymphatic systemDue to developmental due to obstruction of the lymphatic systemShort stature/ short fingers and toesShort stature/ short fingers and toesLoss of ovarian function early in childhood, and thus do not enter puberty Loss of ovarian function early in childhood, and thus do not enter puberty 5-10%- coarctation of the aorta5-10%- coarctation of the aorta30%-bicuspid aortic valves30%-bicuspid aortic valvesHigh blood pressureHigh blood pressureHigh incidence of osteoporosisHigh incidence of osteoporosisType II diabetesType II diabetes/ / hypothyroidismlearning math/

visual-spatial coordination loss Growth hormone & Estrogen therapy

57

Klinefelter’s Syndrome-XXY

Male hypogonadism and infertility somatic and cognitive development are more likely to be affected.

Mental Retardation 1 in 500-1,000 males is born with an extra sex chromosome; more than

3,000 affected males are born yearly Weak muscles and reduced strength Affect different stages of physical, language and social development

58

GERIATRIC MEDICINEGERIATRIC MEDICINE

CHAPTER 4CHAPTER 4

59

GENERAL PRINCIPLES

By age 2030, 20% of the U.S. population will be > age 65.By age 2030, 20% of the U.S. population will be > age 65. Because co-morbidities are common, a disorder in one organ system may lead to Because co-morbidities are common, a disorder in one organ system may lead to

symptoms in another, especially one compromised by preexisting disease, most symptoms in another, especially one compromised by preexisting disease, most commonly of the heart, urinary system, and musculoskeletal system.commonly of the heart, urinary system, and musculoskeletal system.

As such, regardless of the presenting symptom (confusion, falls, etc) the differential As such, regardless of the presenting symptom (confusion, falls, etc) the differential Dx is often the sameDx is often the same

Diseases present atypically.Diseases present atypically. Symptoms are often multifactorial.Symptoms are often multifactorial.

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ASSESSMENT OF OLDER ADULTS

1) FUNCTIONAL ASSESSMENT.1) FUNCTIONAL ASSESSMENT. 2) VISION.2) VISION. 3) HEARING.3) HEARING. 4) FALLS, IMPAIRMENT OF GAIT.4) FALLS, IMPAIRMENT OF GAIT. 5) COGNITION.5) COGNITION. 6) URINARY CONTINENCE.6) URINARY CONTINENCE. 7) DEPRESSION.7) DEPRESSION. 8) DECISION-MAKING.8) DECISION-MAKING.

61

ASSESSMENT OF OLDER ADULTS

FUNCTIONAL ASSESSMENTFUNCTIONAL ASSESSMENT IADL’s-IADL’s- instrumental activities of daily living- bills, shopping, cooking, instrumental activities of daily living- bills, shopping, cooking,

transportation, medication, etc.transportation, medication, etc. ADL’s-ADL’s- activities of daily living- bathing, dressing, eating, etc activities of daily living- bathing, dressing, eating, etc Degree of impairment in IADL’s and ADL’s often dictates the degree to Degree of impairment in IADL’s and ADL’s often dictates the degree to

which THE OLDER PERSON can, and can not, live independently.which THE OLDER PERSON can, and can not, live independently.

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ASSESSMENT OF OLDER ADULTS

FALLS, IMPAIRMENT OF GAITFALLS, IMPAIRMENT OF GAIT Falls- the leading cause of non-fatal injuries in older persons.Falls- the leading cause of non-fatal injuries in older persons. Complications from falls are the leading cause of death in persons over age Complications from falls are the leading cause of death in persons over age

65.65. 1/3 of people over 65 fall each year, this increases w/ each year of age.1/3 of people over 65 fall each year, this increases w/ each year of age. Fear of falling causes many to restrict their activity.Fear of falling causes many to restrict their activity.

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ASSESSMENT OF OLDER ADULTS

COGNITIONCOGNITION Prevalence of dementia doubles every 5 years after age 60.Prevalence of dementia doubles every 5 years after age 60. Some degree of impairment present in 30-50% by age 85.Some degree of impairment present in 30-50% by age 85. Screening can allow for: identification of reversible causes (Vit B12 def); provision Screening can allow for: identification of reversible causes (Vit B12 def); provision

of support services; planning (advance directives, living wills, etc); other of support services; planning (advance directives, living wills, etc); other interventions as appropriate (simplification of medication regimens, etc).interventions as appropriate (simplification of medication regimens, etc).

““Draw a clock” test, 3 item recall. Pg 52.Draw a clock” test, 3 item recall. Pg 52.

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COMMON PROBLEMS OF THE OLDER PERSON 1) DEMENTIA.1) DEMENTIA. 2) URINARY INCONTINENCE.2) URINARY INCONTINENCE. 3) PAIN.3) PAIN. 4) CHRONIC ARHTHRITIS4) CHRONIC ARHTHRITIS 5) POLYPHARMACY5) POLYPHARMACY