A review of progress in cancer prevention, diagnosis and treatment

1. Update in
Oncology
Prof. Shad Salim Akhtar
MBBS, MD, MRCP(UK), FRCP(Edin), FACP(USA),
Member UICC Fellows, Member ESMO, ASCO
Member Global Cancer Control Community, UICC
Overseas Advisor Royal Coll of Physicians, Edin, UK
ICRETT Fellow British Columbia Cancer Agency Canada
Director Hakim Sanaullah Cancer Centre, Sopore, Kmr

2. Hakim Sanaullah Cancer Centre
Rafiabad Kashmir
Hakim Sanaullah Specialist
Hospital & Cancer Centre

5. Topic Outline
What is cancer?
How big is the problem of cancer?
How is cancer caused?
Can cancer be prevented?
Diagnosis of cancer
Early detection of cancer
Treatment of cancer
Treatment of cancer related complications
End of life care

6. Example of Normal Growth
Cell migration
Dermis
Dividing cells
in basal layer
Dead cells
shed from
outer surface
Epidermis

7. Tumors (Neoplasms)
Underlying tissue

8. Loss of Normal Growth Control
Cancer
cell division
Fourth or
later mutation
Third
mutation
Second
mutation
First
mutation
Uncontrolled growth
Cell Suicide or Apoptosis
Cell damage—
no repair
Normal
cell division

9. Invasion and Metastasis
3
Cancer cells
reinvade and grow
at new location
1
Cancer cells invade
surrounding tissues
and blood vessels
2
Cancer cells are
transported by the
circulatory system
to distant sites

10. Malignant versus Benign Tumors
Malignant (cancer)
cells invade
neighboring tissues,
enter blood vessels,
and metastasize to
different sites
Time
Benign (not cancer)
tumor cells grow
only locally and cannot
spread by invasion or
metastasis

11. Cancer its Impact
Malfunction of a cell = disease
Cancer cell
– Malfunction + Strikes its own kind
A cardiac or respiratory illness is
considered a disease of the system but
cancer is the disease of an individual
Cancer diagnosis effects not only the
individual but whole family

13. True or False
Cancer is a major killer
disease of “developing
countries”?
Cancer is a “life style”
disease?

14. Did you know?
–Cancer second leading cause of
death
–Average years of life lost
Cardiac causes 11 years
Cancer 15 years

15. Jemal A et al: Ca Cancer J Clin 2008; 58:71

16. IARC Globocan 2002, Figures based on 1998-2002 prevalence
Burden
of
Cancer

18. Jemal A et al: Ca Cancer J Clin 2008; 58:71

19. Jemal A et al: Ca Cancer J Clin 2008; 58:71

21. All Cause
Mortality
Cancer related
mortality 7.6 million
Developing
countries
Developed
countries
70%
Worldwide Mortality 2005
WHO Cancer Fact sheet number 297

22. New Cancer Cases (Incidence) and Deaths
(Mortality) in 2002.
Parkin DM et al: CA Cancer J Clin 2005;55:74–108
Thousands

23. Parkin DM et al: CA Cancer J Clin 2005;55:74–108
New Cancer Cases (Incidence) and Deaths
(Mortality) in 2002.
Thousands

24. Number of Cancer Cases
Country Male Female Total <14 yrs
India 386,854 426,741 813,595 33%
Pakistan 61,624 75,095 136,719 42%
Bangladesh 39,984 44,090 84,074 35%
Sri Lanka 8,365 9,777 18142 26%
Nandakumar A et al: UICC Strategies for Cancer Control in South Asia-2006, pp17

25. 0.38
0.82
0.46
0.94
0.6
1.2
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2005 2010 2020
Cancer in South Asia
Millions
Mortality
UICC 2006

26. Magnitude of the Problem
New cases in 2020
Future looks GRIM

27. Cancer Related Mortality
Higher than AIDS, TB, Malaria put
together
Second to cardiovascular diseases
Years of life lost more than CV diseases
Increasing definitely

30. Literacy in South Asia
Country Literacy
Male Female
Bangladesh 53.9 31.8
India 68.0 44.0
Nepal 65.1 42.5
Pakistan 54.8 32.0
Sri Lanka 94.8 90.0

31. Survival related to Literacy
Mumbai-India
Yole BB et al: Asia Pacific J Ca Prev 2004; 5:308

32. Country < 1$/day < 2$/day
India 44.2% 86.2%
Bangladesh 29.1% 77.2%
Pakistan 31.0% 84.7%
South Asia Income
Kurkure AP et al: UICC Strategies for South Asia 2006: 26

33. Socioeconomic Status and Breast
Cancer Outcome in Pakistan
Socioeconomic
Status
Stage at
Diagnosis
Treatment Outcome
Early Late Adequate 10 yr Surv
Low 50% 50% 44% 22%
High 75% 25% 89% 73%
Aziz Z. Stigma of Breast Cancer in Developing Countries Costs
Lives: ESMO Newsletter. January –March, 2003

34. Poverty
Lack of
Education
•Lack of compliance
•Prevention
•Early detection
•Treatment
•Follow up
•Late diagnosis

35. Breast Cancer Size vs Survival
0
10
20
30
40
50
60
70
80
90
<2 2 to 5 >5

36. Nature
Nurture
Fate
c
a
n
c
e
r

37. What Causes Cancer?
Some viruses or bacteria
Heredity
Diet
Hormones
RadiationSome chemicals

38. Process of Carcinogenesis
Chemical carcinogen
DNA Adducts
Detoxification
Activation
Excretion
DNA
DNA Repair
Cytochrome P450
DNA Adducts

39. Heredity? Behaviors? Other Factors?
100
50
5
0
Stomach Cancer
(Number of new cases
per 100,000 people)
U.S.Japan Japanese
families
in U.S.
100
70
7
0
Colon Cancer
(Number of new cases
per 100,000 people)
U.S.Japan Japanese
families
in U.S.

40. Cancer Among Female Iranian Migrants
to British Columbia, Canada
Yavari P et al: Asian Pac J Cancer Prev 2006;7:86-90.

41. Risk of Malignant Melanoma
Origin vs Duration of Stay in Israel
0-9
10 to 19
20-29
30+
African
Asian
European
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
African
Asian
European
Duration of Stay in Years
Steinitz R etal: IARC 1989

42. 0-9
10 to 19
20-29
30+
African
Asian
European
0
0.2
0.4
0.6
0.8
1
1.2
1.4
African
Asian
European
Risk of Breast Carcinoma
Origin vs Duration of Stay in Israel
Duration of Stay in Years
Steinitz R etal: IARC 1989

43. Common Cause of Cancer
Sub Saharan Africa Europe
IARC 2000

44. Modifiable Causes of Cancer
Smoking
Alcohol
Overweight & obesity (high income countries)
Low intake of vegetables and fruit
Infections (HPV) (middle & low income
countries)
(others air pollution, fuels, contaminated
injections, physical inactivity)
Goodarz D et al: Lancet 2005; 366: 1784

45. Closed Circular DNA
Viral replication
Persists for life time? during
Ch infection
Random integration into
the host genome
Immortalized cells
Malignant phenotype
Genetic alteration
Inactivates p53, Free
radical & superoxide
prduction, induces
genomic instability
Activates cellular
oncogenes

46. Craxi A et al: Clin Liver Dis 2005; 9:329
Education
Vigorous blood product screening
Aflatoxin prevention as in Sudan

47. Vaccination-Taiwan Experience
Nation wide HBV vaccination program
– Initiated 1984
HBsAg carrier state in children
– Pre vaccination 10%
– Post vaccination 10 yrs <1%
Annual incidence of HCC (per 100,000) in
children 6-14 yrs
– 1981-86 0.70
– 1986-90 0.57
– 1990-94 0.36
Chang MH et al: NEJM 1997; 336:1855

48. Helicobacter pylori organisms
between the domes of epithelial cells

49. Calam J etal. BMJ 2001; 323:980
Relation of H pylori infection to UGI conditions

50. Relationship of H pylori with Gastric Cancer
Development
Uemura Naomi etal. N Engl J Med 2001; 345:784-9
1246 Pts
280 Pts

51. Gastric MALT lymphoma
MALT reacts with the antigen
present within the lumen
CD4+T cells encountering AP
Cells+H pylori antigen
stimulate proliferation of B cells
B cells synthesize
immunoglobulins
Immunoglobulins react with
autoantigens
Parsonnet J et al: N Engl J Med 2004; 350:213

52. Rooney N et al: Curr Diag Pathol 2004; 10:69

53. Rooney N et al: Curr Diag Pathol 2004; 10:69

54. is still a cigarette,
and still as dangerous!
3 times CO and 5 times Tar compared to a cigarette
a cigarette by any other name …

55. Addicting Nicotine
4000 Chemicals
60 Carcinogens
Perfect Killing Machine
Hecht SS: Nat Rev Cancer 2003;3:733

56. At Age 18 At Age 19
Chewing, spitting,
smokeless
tobacco = the “real”
bite
Tobacco
16 to 20% boys
and 2% girls in
high school boys
admit use

58. Betel leaves
Betel nut
Lime

59. Smoking-Related Cancers
• Bladder • Lung
• Cervical • Mouth
• Esophageal • Pancreatic
• Kidney • Throat
• Laryngeal
Increases risk of
Leukemia, sinonasal, nasopharyngeal,
stomach, pancreas, bladder, ureter and
renal pelvis IARC 2002

61. Ardent supporter of anti-smoking campaign and research

62. Copyright ©1996 BMJ Publishing Group Ltd.
Proctor, R. N BMJ 1996;313:1450-1453
"Our Fuhrer Adolf Hitler drinks
no alcohol and does not
smoke.... His performance at
work is incredible." (From Auf
der Wacht 1937:18)
•Ban on smoking in
•Public places
•Transport and restaurants
•Advertising ban
•Increased tobacco taxes
•Ban on sale of tobacco
•Pregnant women
•Women below 25 yrs
• Major publications
•Confirming the relationship
of smoking and lung cancer
Anti smoking activities in Nazi
Germany

63. CertificateofParticipation
This is to certify that_______________________ has participated in the declamation contest titled
“Tobacco Free Kashmir: bringing the dream to reality”,
held on the 6th of November 2007 and has secured the Third Prize.
Prof. Shad Salim Akhtar Prof. M Y Shah
Chairman Board of Directors Professor and Head
Hakim Sanaullah Specialist Hospital & Cancer Centre Dept. ofPharmaceuticalSciences, KU
Hakim Sanaullah Specialist Hospital &
Cancer Centre
Sopore, Kashmir
Department of Pharmaceutical
Sciences,
University of Kashmir
TOBACCO FREE Kashmir
bringing the dream to reality
6 T H
NOV EMBER 2007, C ANCER AWAR E NESS DAY EV E, I QBAL LIBRARY AUDI TO RIUM, KU

65. Anderson LD et al: The Oncologist 2002; 7:200
Smoking cessation
Early detection
Screening
Dietary changes
Cancer Mortality 1990
vs 2000 USA

66. Cancer screening-What is the
aim?
Detect asymptomatic potentially curable
disease
– Earlier than otherwise would occur
– Earlier diagnosis should result in improved
outcome
Reduce morbidity and mortality from a
particular cancer in screened population
Reality xelpmoc (COMPLEX)

67. Suitable cancer for screening
Substantial morbidity & mortality
Major disease burden
High prevalence in a detectable preclinical
phase
– Sojourn time
Early detection should lead to improved and
effective therapy
A good screening test should be
available

68. Ideal Screening test
Should separate the two populations
– Apparently well with the disease
– Those who do not have the disease
Acceptable
Inexpensive
High specificity and sensitivity
Least inconvenience and discomfort
Feasible for use in large numbers
Kramer BS. NCI 1995

69. Is there a tiger?
NO NO NO NO
SENSITIVITY
SPECIFICITY
YES YES YES YES

70. Screening- Recommended sites
Females
– Breast
– Endometrium
– Cervix
Males
– Prostate
Both sexes
– Colorectal
– Cancer related check up
American Cancer Society 2004

72. Cancer Patient Management
Diagnosis
Stage of disease
Prognostication
Treatment plan
Complications Early/Late
– Treatment
– Disease
Long term follow up
Supportive care

73. Screening
Diagnosis
Surgery
Adjuvant therapy
Quality of life
Chemotherapy
Radiotherapy
End of life-care quality

74. Detailed history
Elucidate complications
– Effect on other organ systems
Physical examination
– Special attention to possible spread
– Lymph nodes
– Lung
– Liver
– Bone
Cancer Patient Management

75. How is Cancer Diagnosed?
Invasive tissue biopsy
– Histology
– Grade
– Invasiveness
– Molecular information
– Cell surface markers
FNAC
– Like thyroid nodule
– Breast lump
Look for a primary if pt presented with
metastatic disease

76. Cancer Investigations
CBC
Chemistry
– LFT
– KFT
– Protein estimation
Bone marrow aspiration or biopsy
Tumor markers
Other biochemical markers
Endoscopic examination

77. Cancer Imaging
X-rays
Mammograms
Radionuclide scan
Ultrasound
CT Scan
MRI
Other imaging investigations

78. PET
Sca
n

79. Persistent Non-Hodgkin’s Lymphoma
Juweid ME and Cheson BD. N Engl J Med 2006;354:496-507

80. Early Detection of Persistent Hodgkin’s Disease
Juweid ME and Cheson BD. N Engl J Med 2006;354:496-507

81. Early Detection of Recurrent Cervical Carcinoma
Juweid ME and Cheson BD. N Engl J Med 2006;354:496-507

82. Private Institutions-the conflict?
Patient autonom
Profit

83. Cancer Staging
TNM
–Tumor
–Nodal status
–Metastasis
FIGO
Ann Arbor
Duke’s
Stage 1 to 4

84. Cancer Treatment
Local
Surgery
Radiotherapy
Chemotherapy
Laser

85. Cancer Treatment
Systemic
Chemotherapy
Hormone therapy
Biological response
modifiers
Gene therapy

86. Chemotherapy
Mechanism of Action
 Macromolecular synthesis
& function
 Cytoplasmic organisation
 Cell membrane synthesis
function

87. M
G2
S
GIB
Daughter
Cell
Irreversibly
Differentiated
Cell
GO
Prolonged
G1
G1A
Amount
of DNA
Tetraploid
Di- ploid
DNA Synthesis

88. G (resting)0
16 - 20
S
DNA synth
18 - 30
G1
RNA and
protein synthesis
Phase
Function
Duration
(hrs) 2-10
RNA &
PS
0.5-1
M
Mitosis
G2
Differentiation or
continued replication
Cell cycle - Kinetics

89. D N A
RNA
Protein
Tubulin
Salv pathwayDe novo synth
Purines
dTMP
dCMP
FH4
FH2
CMP
dUMP
Transcription
Free rad dam
Strand breaks
Alkylation
Intercalation
Translation
Bleomycin
Etoposide
Teniposide
Dactinomycin
Adriamycin
Daunomycin
Adriamycin
Daunomycin
Ara-C
Flud
5FU
5FU
Vincristine
Vinblastine
Taxanes Estramustine
6-MP
6-TG
Mechlor
Cyclo
Ifosf
Melpha
Carbop
Cispla
Nitro
Proca
Dacar
Methotrexate
L-Asparaginase
Topoisomerase 1
inhibitors
Irinotecan

90. Chemotherapy-Types
Phase specific
G2 Phase
Etoposide
Bleomycin
Taxol
M Phase
Vincristine
Vinblastine
Vindesine
G0 Phase
G1 Phase
L-Asparg
Steroids
S Phase
Antimetab
Hydroxyurea
Cell cycle specific

91. Chemotherapy Types
Cycle specific Cycle non specific
Phase non specific Phase non specific
Steroids
Alkyl. agents
Procarbazine
Dacarbazine
Streptozotocin
Alkylating
agents
Dactinomycin
Anthracyclines
5-Fluorouracil

92. 1012
1010
108
10
6
104
102
NumberofCells
Doublings
1mg
1 g
Days 40 80 120 160
22 22 4020 3010
1g
1 kg

93. 10
10
10
10
10
10
12
10
8
4
2
2 3 54 6Begin
(Clinical Complete Response)
< 10 Cells9
(Complete Tumor
Eradication) < 1 Cell
Time
TumorSize
(CellNumber)
Cycles
6
All cells sensitive
Drug accessibility
uniform
No change in cell
sensitivity.
Assumption

94. Necrotic
Fraction
Non Proliferative
(Avascular)
Fraction
Proliferative
Fraction
Differentiated
Fraction Fraction
G0
Metastases

95. Chemotherapy
Combinations--Why?
Prevention of resistant clones
Cytotoxicity to resting
and dividing cells
Biochemical enhancement of
effect
Rescue

96. Chemotherapy
Indications
 To cure certain malignancies
 To palliate symptoms
 Treat aggressive cancer in
asymptomatic patients
 Adjuvant therapy

97. Chemotherapy
Contraindications
 Lack of facilities to monitor
response and side effects
 Expected survival shorter than
required for reponse
 Asymptomatic pt with slow
growing incurable tumor
 Expected survival shorter than
required for benefit of therapy

99. Chemotherapy
Administration
Preparation
Laminar flow
Aseptic technique
Personal care
Compatibility
Storage
Concentration
Route of administration

100. Chemotherapy
Administration
Vein selection
Large forearm veins
Dorsum of hand
Exercises
Avoid
Antecubital fossa
Wrist
Covering the cannula tip

101. New Therapeutic Modalities
Immunotherapy
–Vaccines
–Cell transfer therapy
Targeted therapy
–Receptor bases therapy
Anti-angiogenesis therapy

102. Cancer Vaccines
Lymphoma
Gastro intestinal cancer
Prostate cancer
Melanoma

103. Rosenberg SA NEJM 2004; 350:1461
Lymphocytes:
Sufficient
number of
recognizing
tumor cells
Reach the tumor
Must be able to
destroy the
tumor cells

105. Lymph nodes of Pts from Dutch Trial ASCO Presentation

106. TARGETTED
THERAPY

107. Targeted Therapy
MOA against cell surface markers
– Lymphoma cells (like anti CD20)
Receptor based therapy
– Estrogen receptors
– Tyrosine kinases
– RAR
– EGF
– VEGF
Proteasome inhibitors

108. Estrogen
biosynthesis
Tumor cell
Nucleus
Inhibition of
Estrogen Dependent Growth
Inhibition of
cell
proliferation
Estrogen
biosynthesis
Antiestrogens
Aromatase
inhibitors

109. Chromosomal Abnormality
90-95% pts have
this translocation

110. Krause DS et al: N Engl J Med 2005; 353:172

112. Cell surface
HER2 protein
(HER2 receptor)
Other EGFR/HER
family receptor
Cell nucleus

113. Activated HER2-HER2 dimers
Growth signal
Cell nucleus

114. Tumor cell growth

115. Herceptin monoclonal
antibody

116. Response Usually a response is result of a
stimulus or a reply to a query
In the context of cancer we
mean response to therapy
Complete
Partial
Stable disease
Progression

117. Cancer
No Fever
Fever
No
Cancer

118. Follow the Mass!!
Is this patient in CR?
At Presentation After Chemotherapy

119. All That is >1 cm is Disease?
Necrosis
Inflammation
Fibrosis
Matted Group of Nodes

120. Chemotherapy
Ideal Agent
Lethal Action on
cancer cells
No effect on host
cells

121. CytotoxicEffect
Plasma Drug Concentration
Normal Tissue
Response
Tumor
Response
100
50

122. LIVER KIDNEY EXCRETED
EXCRETED
LYMPHATICS
EXTRACELLULAR
COMPARTMENTS
COMPARTMENTS (N or T)
BILE
INTRACELLULAR
BLOOD
CELLS
GUT
I/V --> PLASMA

123. Therapy
Advanced cancer
Common Complications
of Cancer

124. Common Complications of Cancer
Acute
–Nausea, vomiting
–Diarrhoea
–Extravasations
–Hypersensitivity reactions
Therapy related

126. Immediate
– Alopecia
– Haematological
Febrile Neutropenia
– Pulmonary toxicity
– Neurological
– Gastrointestinal
– Renal
– Hepatic
Late
– Cardiac
– Reproductive
Common Complications of Cancer
Therapy related

131. Could be a medical emergency
Fever >380 (2 spikes) or 38.50
Elderly patients may react differently
ANC <500 or rapidly falling
Assess general condition of the patient
Infection screen
Broad spectrum antibiotics
Common Complications of Cancer
Febrile neutropenia

134. Common Complications of Cancer
Neurological
Skeletal
Haematological
Gastrointestinal
Endocrine
Respiratory
Effusions
–Increase with disease progression
Advanced cancer

135. Oncological Emergency Definition
Requiring treatment immediately to avoid
mortality or severe permanent morbidity

136. Nature of Emergency
Circulatory
Respiratory
Neurological
Metabolic
Others
– Infections
– Reaction to drugs
– Bowel perforation

138. Superior
Mediastinum

139. Partial or complete obstruction of blood flow through
SVC to Right atrium
SVC Syndrome What is It?

140. SVC Syndrome
What Causes It? Mechanism
Compression
Invasion
Thrombosis
Fibrosis

141. SVC Syndrome - Causes
Lung cancer
– SCLC
– NSCLC
Lymphoma
– NHL
Primary mediastinal
malignancies
– Germ cell tumors
Metastatic disease
– Breast cancer

142. SVC Syndrome- Symptoms
Symptoms % Pts affected
Dyspnoea 63
Facial swelling 50
Head fullness 50
Cough 24
Arm swelling 18
Chest pain 15
Dysphagia 9
Thirwell C et al. Clin Med 2003; 3:306

143. Physical finding % Pts affected
Neck vein distension 66
Chest wall vein dist 54
Facial edema 46
Cyanosis 20
Facial plethora 19
Arm edema 14
SVC Syndrome- Signs
Severity of symptoms relates to rate of obstruction
Thirwell C et al. Clin Med 2003; 3:306

144. SVC Syndrome- Investigations

147. SVC Syndrome-Investigations
Chest X-ray
CT scan spiral
MR venogram
CT guided biopsy
Emphasis has shifted from
prompt treatment to prompt
diagnosis

148. Emergency RT
reserved for
impending
airway obst or
raised ICT

149. Common Complications of Cancer
15-20% patients affected
Epidural cord compression
Raised intracranial pressure
Status epilepticus
Intracerebral haemorrhage
Delirium
Neurological

150. Epidural Cord Compression
Compression of thecal
sac by tumour
– Spinal cord
– Cauda equina
One of the most common
neurological emergencies
in oncology
App 5% of all cancer pts
affected
Incidence increasing with
improved survival

151. Cervical (10)%
Thoracic (70%)
Lumbosacral (20%)
10-38% multiple non-contiguous sites
Lung
Breast
Colon
Pelvic
Location
Epidural Cord Compression

152. Clinical features
Epidural Cord Compression
Pain
– First symptom in 96% pts
– Median duration ~7 wks (hrs to months)
– Localized initially to back
– Midline

153. Pain
May mimic disc disease except:
– Exacerbated by recumbence
– Improves by upright position
Radicular
– Less frequent
– Localizing
Referred
Epidural Cord Compression

154. Neurological dysfunction
– Three quarters-weakness
– 50% --sensory loss+autonomic
Weakness
– 2nd most common symptom
– Typically lower limbs
Irrespective of site
– Proximally more marked
– Paraplegia may be abrupt
Epidural Cord Compression

155. Diagnosis
MRI the best diagnostic tool
Myelography under special circumstances
Image the entire spine
High index of suspicion
Epidural Cord Compression

156. MRI in Cord Compression

157. Normal looking cord

158. Cord Compression

159. CT guided biopsy

160. What Is It?
Ca+ + level
>10.3mg/dl
>2.57mmol/l
Total
Ionised
>5.1mg/dl
>1.27mmol/l
A symptomatic pt with normal total Ca level
Malignant Hypercalcemia

161. 1% of all ca pts suffer from HiCa
Ca mobilisation exceeds renal threshold
Causes in ambulatory vs. Hospitalised pts
Tumour assoc HiCa caused by osteolysis
80% with malignant HiCa have bone mets
– 80% osteolytic
PTHrP may be produced without bone
mets
What Causes It?

162. Increased bone destruction
Increased tubular re-absorption of
calcium by the kidney
Decreased urinary calcium
excretion
Decrease in bone formation
Hypercalcemia Mechanism

163. Breast ca
Bronchogenic ca
Renal cell ca
Multiple Myeloma
Thyroid ca
Sq cell ca H & N, oesophageal and
ovarian ca without osseous mets~
What Causes It?

164. Is hypercalcemia always symptomatic?
Early symptoms nausea anorexia &
vomiting
Constipation
Polyuria
Permanent renal tubular damage may
occur
Myocardial instability may cause
arrhythmias/sudden death
Neurological symptoms may predominate
Hypercalcemia Symptoms

165. Severe Hypercalcemia
Serum
total ca
(mmol/L)
4
3
2
16
12
8
(mg/dl)
Normal range for Serum calcium
Moderate Hypercalcemia
Mild Hypercalcemia
Normocalcemia
Mild hypocalcaemia
Serum
total ca

166. Decrease oral intake of ca??
Promote urinary excretion
Decrease bone resorption
Antitumor therapy
Hypercalcemia Therapy

167. Fluid deficit
Which fluid---normal saline
300-500 ml/hr initially
May need 3-4 litres in 24 hrs
Saline diuresis 100-200 ml/hr
Add frusemide once hydrated
Hypercalcemia Therapy
Hydration

168. Improves renal handling of ca only
Aggressive fluid therapy assoc with high
morbidity
May need ICU monitoring
Hi ca may not be corrected
Hypercalcemia Therapy
Hydration

169. Corticosteroids
Bisphosphonates
Cacitonin
Gallium nitrate
Mithramycin
Hypercalcemia Therapy
Decreasing bone
resorption

170. Bind to hydroxyapatite crystals in bone
matrix
Inhibits dissolution
Blocks maturation of osteoclast
Osteoclast apoptosis
Affect the signalling pathway between
osteoblasts & osteoclasts
HypercalcemiaTherapy
Bisphosphonates

172. Anemia in cancer-
Causes
Disease related
Therapy related
Concomitant factors

173. Disease related causes-
Cytokine Mediated
Tumor
cells
Activated immune & inflammatory system
Cytokines
Hepcidin levels ?
Other
effects
Reduced erythropoietin
production
Impaired iron
utilization
TNF IFN- IL1
Down regulation of EPO-R
Suppression of
BFU-E/ CFU-E
Anemia
Mercandante S et al: Cancer Treat Rev 2000;26:303-11

174. Shortened
RBC survival
Anemia
Blood loss
Disease related causes
- others
Disrupted
homeostatic
mechanisms
Tumor
cells
Reduced
erythropoietin
production
hematopoeitic cell
clonal disorder
Hemolysis
Hemophagocytosis
Hypersplenism
MAHA
Marrow infiltration
Consumption
Deficiencies
Intercurrent infections
Mercandante S et al: Cancer Treat Rev 2000;26:303-11

175. Anemia-effect on
the patient?
Physiological response
Cancer related fatigue
–A common symptom (58-90% pts)
–Associated with anemia?
Increased mortality
Effect on treatment efficacy

176. Ferrario E et al: Cancer Treat Rev 2004; 30:563-75

178. Cancer Related Pain
At diagnosis 25%
Advanced disease 75%
During therapy 30%
Goudas LC et al: Cancer Invest 2005;23:519

179. Barriers to Pain
Management

180. Palliative Care Problems-
Medical Personnel
Lack of awareness
prevents delivery
Dissemination of
information
Opiophobia Education
Imitation of western
models of care
Develop local
strategies
Seamark D et al: J R Soc Med 2000; 93:292

181. Palliative Care Problems-Public
Lack of
awareness
creates delays in
seeking palliative
care
Public
education
Seamark D et al: J R Soc Med 2000; 93:292

182. Palliative Care Problems-
Social/System
Silence about cancer
diagnosis
Discuss cancer diagnosis
openly
Poverty Consider financial condition
of the patient while
prescribing
Coexistence of multiple
systems of medicine
Work together as partners
not rivals§
Transport problems Support private sector to
create rural centers Involve
relatives
Non availability of opioids Public pressure
Seamark D et al: J R Soc Med 2000; 93:292

183. Neurophysiology
Nociceptive receptors
– Myelinated fibres
Noxious mechanical stimuli
Rapid conduction
A delta fibres- sharp stinging pain
– Unmyelinated fibres
Chemical stimuli
Mechanical stimuli
Thermal stimuli
C fibres- dull burning aching pain

184. Cancer Pain Classification
Nociceptive (skin, viscera, muscles,
connective tissue)
– Somatic pain
Most common type
Bone metastasis most common cause
– Visceral pain
Commonly refd to cutaneous sites
Neuropathic pain
Injury to peripheral or CNS
Caraceni A et al: Oncology 2001;15:1627

185. Morphine requirement - India
Total produced 142.32 kg/yr
ONLY 0.4% of the required amount
PRODUCED
Rajagopal MR et
al: J Pain Control
2007;33:615

186. WHO Three - Step Approach

188. 1 Regional 10-12th May 2006
1 International 11-12th Sep 2007
3rd International 1st and 2nd May 2009