This document discusses tumors and transplantation. It begins with classifications of benign and malignant tumors in different tissues. It then covers etiology of cancer including chemical, physical, viral and dietary agents. Stages of cancer development and methods of diagnosis, grading, staging and spread are described. Treatment modalities including surgery, radiation, chemotherapy, hormone and immunotherapy are summarized. The document concludes with principles of transplantation, immunological basis, organ matching, indications and complications of common transplant procedures including kidney and liver transplantation.

1. Tumors & transplantation
By dr. Hori

2. Histogenic classification of tumors
Benign Malignant
Epithelia tumor
-squamous epithelium
-columnar epithelium
-transitional epithelium
-papilloma
-adenoma
-papilloma
-squamous cell carcinoma
-basal cell cercinoma
-adenocarcinoma
-transitional cell carcinoma
Connective tissues
-adipose
-fibrous
-cartilage
-bone
-smooth muscle
-striated muscle
-lipoma
-fibroma
-chondroma
-osteoma
-leiomyoma
-rhabdonmyoma
-liposarcoma
-fibrosarcoma
-chondrosarcome
-chondrosarcoma
-osteosarcoma
-rhabdomyosarcoma.

3. Histogenic classification of tumors
Benign Malignant
Neuroectoderm
-nerve cell
-melanocytes
-meninges
-nerve sheeths
-ganglioneuroma
-pigmented nevus
-meningioma
-neurofibroma
-neuroblastoma
-malignant melanoma
-malignant meningioma
-neuroflbrosacoma
-hemopoietic &
lymohoreticular tissue
-blood vessels
-lymph vessels
-hemangioma
-lymphangioma
-leukemias
-lymphomas
-hemangiosarcoma
-lymphangiosarcoma

4. Etiology of cancer
1-onchogenesis
Agents that damage genes the initiate the malignant transformation.
1. chemical agents
2. physical agent
3. viruses
4. diet
2-another category:
Agents not damage genes but enhance the growth of tumor cells.
hormones
1.Estrogen stimulate growth of cancer breast
2. Androgen stimulate growth of cancer prostate

5. Etiology of cancer
.
3.chemical agents:
a.tobocco smoke (mainly of cigarettes)
e.g.cancer lung,esophagus,urinary bladder&
b.occupational agents:
e.g. –asbestosmesothelioma of lung
- aromatic aminestransition cell carcinoma
of urinary bladder
4.physical agents
a.mechanical irritation:
e.g.gall stonescancer gall bladder.
b.ionizing radiation:
e.g. a & b rays cancer in man &animal
c.ultraviolet rays:
e.g.cancer skin

6. Etiology of cancer.
5.Viruses
a.Human papilloma viruses
sexually transmitted cancer cervix & anus.
b.Hepatitis b & c hepatocellular carcinoma.
6.Diet
a.fatcancer colon & rectum.
b.Alcoholcancer upper digestive tract &hepatocellular
carcinoma.

7. Stages of cancer development
1. Hyperplasia: the cell look normal but reproduce
to too much cell.
2. Metaplasia: change of type of epithelium into
anther type.
3. Dysplasia: the cell becomes atypical in size &
shape.
4. In situ : the cells not invade the basement
membrane.
5. Invasion: the cells begin to invade the
neighboring tissue.
6. Metastasis: the cells tend to reach blood &
lymphatic.

8. Grading of cancer
Grading in a measure for tumor aggression.
-well differentiated tumors : the least aggression.
-moderately differentiated tumors: the most
aggression.
Staging of cancer (TNM)
(t)=extent of 1ry tumor in size & depth.
(n)=presence or absence of LN metastasis.
(m)=presence or absence of metastasis.

9. Spreading of cancer
Properties that allow metastasis
1. Defective cell adhesions: cancer cell lack of
adhesive proteins which bind the cells to
another.
2. Tumor angiogenesis: cancer cells access to
circulation through newly formed capillaries.
3. Production of proteolytic enzymes: which
digest the basement membrane allowing
invasion.

10. Mode of metastasis
1. Local spread : to neighboring organs & tissues.
2. Lymphatic spread : 2 type permeation:
malignant cell invade the endothelium of
lymphatics then grow inside the lymph vessels
embolization: malignant cell invade to
capillarias as an emboli to draining LNs.
3. Blood spread: malignant cells invade to
capillaries as an emboli to lung, bone,liver, &
brain.
4. Transcoelomic spread : travel along cavities
e.g. peritoneum.

11. Diagnosis of cancer
A. Screening
Some people may have a higher risk of developing a
certain malignant tumor.
So certain screening programs are done to detect
the neoplasm as early as position.
A common example is to do soft tissue
mammography for females who have a higher
 chance of developing breast cancer.
B. radiological.
-Various radiological techniques including contrast
studies, ultrasound & CT.

12. C. Endocopy
- This is very useful for diagnosis of the respiratory
gastrointestinal and urinary.
D. Histology
- Needle or operative biopsies essential for tissue
diagnosis.
E. Cytological examination:
- Fine needle aspiration cytology is now a well
established line of investigation which is commonly
used to diagnose lesions of the thyroid, breast.
F. Tumor markers
- Many malignant tumors secrete certain oncofetal
proteins which can be established. This may help in the
diagnosis of certain tumors.

13. Tumor marker Examples included:
1. œ-feto-protein is raised in hepatocellular
carcinoma & testicular tumor.
2. CEA (Carcino-Embryonic Antigen) is raised
with cancer colon & stomach.
3. Prostatic specific antigen is raised in prostatic
carcinoma.
4. CA-15-3 is raised in carcinoma of the breast.
5. CA 125 is raised in carcinoma of the ovaries.
6. CA 19-9 is raised in carcinoma of colon.
7. Thyroglobulin is raised in carcinoma of thyroid.

14. Treatment of cancer
a) Early ( potentiolly curable, operable ) cancer
- Treatment is radical
- Adjuvant “ complementary) treatment of systemic
modalities such a chemotherapy is indicated if there is a
high possibility of systemic microscopic spread in distant
sites.
b) Late ( incurable, inoperable) cancer
- There are distant metastases
- Cure is not possible
- Treatment aims to palliate of the patients symptoms so as
to provide him with a reasonable life quality.
- Treatment is also essentially by systemic modalities as
chemotherapy and hormones.
- Surgery or radio-therapy is sometimes needed to palliate
local symptoms

15. Treatment cont….
The individual modalities of treatment include :
1. Surgery
primary tumor
- Radical surgery aims at excision of the primary tumor
with as wide a safety margin.
Lymph nodes
the treatment of lymph nodes varies from tumor to
another:
-G.I.T malignancies; lymph nodes are routinely resected.
-Breast cancers: they are either resected or irradiated.
- Head and neck malignancies; the nodes are treated only
if they prove to contain malignant deposits.

16. Advantage
Surgical excision is both quick and effective.
Disadvantages
Surgery may produce functional and somatic
disabilities.

17. 2- Radiotherapy
indications
1- cancer of the larynx so as to preserve the voice.
2- early cancer of prostate and early cancer of breast.
Methods
1- powerful x-rays gamma rays, electrons, or heavy
particles are directed to the tumor.
2- the radiation may be aimed at a tumor from outside
the body (teletherapy) or it may be delivered by placing
radioactive needles at the cancerous site ( Brachytherapy).

18. Radiation
• Advantages
1. Curing the cancer without sacrificing the
patients ability to function.
2. Radiation can destroy microscopic extensions
of cancerous tissue around that a tumor that a
scalpel might miss.
3. Radiation is a safer option for older.

19. Radiotherapy
• Disadvantages
1. Some tumors as squamous cell carcinoma are
sensitive but adenocarcinoma is much less
sensitive.
2. Radiation is commonly associated with burns
of the skin or enteritis which are difficult to
treat.
3. Compared to surgery, radiotherapy is slow as
it usually takes 5 to 8 weeks.

20. 3- chemotherapy
Indications
1- main line of treatment of leukemia
2- metastases
Method
- Better results are obtained from combination
chemotherapy rather than using one agent.

21. Hormone therapy
• Examples are
1. anti-estrogen with cancer breast that is +ve
for estrogen receptors.
2. Anti-androgen with cancer prostate.
3. Thyroxin to suppress TSH for patient with
papillary cancer thyroid.

22. 5- Immunotherapy
Non-specific
the tuberculosis vaccine BCG stimulates the
immune system as in transitional cell carcinoma
of the urinary bladder.
Specific
this method is still of limited use.

23. Transplantation
By Dr.hori

24. Transplantation

25. "PRINCIPLES OF Transplantation Surgery"
At the end of this presentation students should be
able to:
 Define terminologies used in organ transplantation
 Describe the immunological basis of organ
transplantation, organ matching, &
immunosuppression.
 Summarize indications, contraindications, and outcome
of common organ transplantation.

26. Transplantation
When no alternative treatments are available
Improves quality of life Improves survival
Needs cooperation of several disciplines-
surgeons, anesthetists, immunologists &
physicians

27. Organ transplantation

28. Two main obstacles to transplantation
Recipients immune response & Shortage of donor organs
Terminology:
 Autograft: Free transplantation of tissue from one part
of the body to another in the same individual.
 Isograft: Transfer of tissue between genetically
identical individual- identical twins.
 Allograft: Organ transplanted from individuals of same
species- main class of transplantation in humans
 Xenograft: Organ transfer between dissimilar species.
Tissue is chemically treated to make it non-antigenic
(porcine heart valve).

30. Terminology
• Orthotopic graft: Donor organ transplanted to the
diseased organ site- liver.
• Heterotopic graft: Donor organ transplanted at a
site different from normal anatomical position
Kidney in iliac fossa.
• Artificial (hybrid) organ implantation: Bio-artificial
organs (combination of biomaterials & living cells)-
experimental technique
• Donor organs Cadaver graft: Organ retrieved from
an individual pronounced dead according to a
defined criteria.
• Living donors:-Related - parent or siblings-
Unrelated - voluntary or to make money

31. Immune response Auto & isografts -
do not elicit immune response.
• Inflammation- center of rejection process.
Reperfusion→ endothelial activation→
infiltration of inflammatory cells particularly
macrophages.
• Major histocompatibility complex (MHC)-
encodes transplant antigen which are similar to
serum HLA (human leukocyte antigen)

32. Afferent arm of immune response
 Presentation of donor MHC antigen to recipient
T-cells receptor (TCR) leads to T-cell activation.
Recognized as foreign by recipient T-cells.
Clonal expansion of T-cells.
Differentiation T- cells into:CD4 positive (helper):
Helping B-cell → plasma cells to make antibody,
and activate phagocytosis.
CD8 positive (effector)- Control level and quality
of immune response.
CD4- central role in rejection process.

33. Efferent arm of immune response
Donor organ damage- efferent arm response.
Humeral mechanism- antibody produced by B-
lymphocytes (under influence by cytokines
released by T-cells CD4).
Cellular mechanism- by cytotoxic T-cells,
macrophage, natural killer cells (large granular
lymphocyte) & neutrophils.

34. Clinical patterns of rejection
Hyperacute: Within 24 hours due to
preformed antibody (IgG) against donor HLA
antigens Overcome by pre-transplant
screening.
Acute: within 6 months in up to 50% grafts.
Characterized by infiltration of activated T
cells and inflammatory cells.
Chronic: >6 months, progressive decline in
function. Multifactorial damage-(immune
mediated, toxicity from immunosuppression,
viral infection) cellular atrophy, fibrosis.

36. Organ matching Donors & recipients are
tested for:
 ABO compatibility: ABO red cell antigen is also
expressed on most tissue cells.
HLA tissue typing: HLA antigen class 1 & 2 tested
on the donor and recipient lymphocytes.HLA
typing most useful in renal transplant.
Direct cross match- incubating donor
lymphocyte with recipient plasma.
Detects preformed antibodies.

37. Organ retrieval Cadaver: Heart beating,
ventilation supported
Retrieval after cardiac arrest, rapid organ
perfusion
Organ function in donors established. e.g.
Kidney Normal urine output (except oliguria
due to dehydration), analysis, urea &
creatinine.
Live related: Kidney, liver, pancreas, lung,
small intestine Must justify operative risk.

38. General contraindication to organ donation
 Age > 90
 HIV disease
 Disseminated cancer
 MelanomaTreated cancer within 3 years of donation
 Neurodegenerative disease due to infection- CJD
Organ specific contraindication to organ donation
 Liver: Acute hepatitis, cirrhosis, portal vein thrombosis.
 Kidney: Chronic kidney disease, long term dialysis, renal
malignancy, previous renal transplant.
 Pancreas: Insulin dependent diabetes, pancreatic
malignancy

39. Immunosuppression
Achieve a balance between prevention of rejection and morbidity-side
effects, risk malignancy.
1. Steroids: 1st line for acute rejection. Side effects of long term use.
2. Azathioprine (AZA): For acute cellular rejection in renal transplant
Myelosuppression, GI symptoms.
3. Mycophenolate mofetil: Prevents lymphocyte activation, replaced
AZA in renal transplant
4. Calcineurin inhibitors: Cyclosporin- acts by inhibiting cytokines
which activates lymphocytes. Nephrotoxicity, hypertension,
hyperglycemia, hyperlipidemia.
5. Tacrolimus- Better outcome in kidney & liver transplant.
Nephrotoxic, neurotoxic, diabetes, alopecia.
6. Sirolimus: Inhibits T cell activation. Limited use due to toxicity
7. Antibody: Induction therapy at the time of transplantation to
provide immediate immunosuppression after transplantation.(
antithymocyte globulin, alemtuzumab, interleukin-2 antibody)

41. Complications of immunosuppression
1. Susceptibility to infections: TB, candida, pneumocytis
carinii, cytomegalovirus, EB virus, measles, herpes.
2. Risk of malignancy: SCC, Lymphoma Specific side
effects of individual agent or regimen.
Organ donation Deceased donation- according to
country rules
1. Donor management: Cardiovascular stability, and
maintaining organ function- optimal fluid, maintaining
BP, & minimal inotrope support.
2. Organ preservation: Cold storage by intravascular
flush with chilled preservation fluid- UW fluid
(University of Wisconsin) or Eurocollins solution.
3. Preservation time- Kidney 24 hrs. , liver 20 hrs.

43. Renal transplantation
Indication:
End stage renal disease
Patient assessment:
1. Absolute contraindications- malignancy, active
infection.
2. Relative contraindications- advance age, severe cv
disease, non-compliance with immunosuppressive
therapy.
3. Diabetes, hypertension, amyloidosis can also affect
the transplanted kidney.
4. Outcome: 1- year graft survival 90% , 5- year graft
survival 70%, Peri-operative mortality- 2-5%

44. Renal transplant

45. Liver transplantation
Indication:
• Chronic liver disease with signs of
decompensation (OV, ascites, jaundice,
coagulopathy, SBP, hypoalbuminaemia)
• Common aetiology : Adults- alcohol, HBV, HCV,
primary biliary cirrhosis, sclerosing cholangitis,
HCC, acute liver failure due to paracetamol
toxicity, viral Children- biliary atresia, Wilson’s
disease.
• Patient assessment: Expected 50% chance of 5
year post-transplant survival.

46. Liver transplantation

47. Liver transplantation
1. Living donor: A portion of liver removed for transplant
in children or small recipient.
2. Donor liver regenerates to full size and function.
3. Donor mortality- 0.5%.Post-op.
4. Management of rejection: Usually around day 7- rising
transaminases.
5. Biopsy to confirm rejection. Treated b
methylprednisolone for 3 days.
6. Complete rejection rare.
7. Outcome: 1 year survival 90%, 5-year survival 66%
Need for long term immunosuppression Most patients
report good quality of life.

49. Pancreas transplantation
Indication: Type I diabetes mellitus
SPK – simultaneous pancreas- kidney transplant
PTA- pancreas transplant alone
Outcome: 1-year pancreas graft survival 82%.
Pancreatic islets cell transplantation- more then
one pancreas is needed to treat one patient.

50. Heart transplantation

51. Heart & lung transplant
Heart: Coronary related heart failure,
cardiomyopathy, valvular disease, congenital
HD.
Lung: COPD, cystic fibrosis, pulmonary fibrosis.
Most challenging of all transplants.
Outcome:
Heart- 65% at 5 years, 50% at 10 years & 30% at
15 years.
Lung- 50% at 5 years and 25% at 10 years.

53. END OF THE LECTURE