Oncology: basic science for general surgical residents, Thailand facebook: happy friday knight

1. ONCOLOGY
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Basic Science for General Surgical Residency Program
Thailand

3. • Neoplasia (new growth): uncontrolled
proliferation of transformed cells
• The surgeon often is responsible for the initial
diagnosis and management of solid tumor

4. • Primary surgical therapy refers to en bloc resection of
tumor with adequate margins of normal tissues and
regional lymph nodes
• Adjuvant therapy refers to radiation and systemic
therapies, including chemotherapy, immunotherapy,
hormonal therapy, and biologic therapy
• The primary goal of surgical and radiation therapy is
local and regional control and for systemic therapy is
systemic control by treatment of distant foci of
subclinical disease to prevent distant recurrence

5. Epidemiology
• Incidence: new cases per 100,000 persons per
year
• Mortality: deaths per 100,000 persons per year

6. Most common cancer worldwide
• In men
1. Lung
2. Prostate
3. Colorectal
4. Stomach
5. liver
• In women
1. Breast
2. Colorectal
3. Cervix
4. Lung
5. stomach

7. สถาบันมะเร็งแห่งชาติ กรมการแพทย์กระทรวงสาธารณสุข. ทะเบียนมะเร็งระดับโรงพยาบาล พศ.2555.
กรุงเทพ: โรงพิมพ์ตะวันออก, 2557. หน้า 1.

8. สถาบันมะเร็งแห่งชาติ กรมการแพทย์กระทรวงสาธารณสุข. ทะเบียนมะเร็งระดับโรงพยาบาล พศ.2555. กรุงเทพ: โรง
พิมพ์ตะวันออก, 2557. หน้า 3.

9. สถาบันมะเร็งแห่งชาติ กรมการแพทย์กระทรวงสาธารณสุข. ทะเบียนมะเร็งระดับโรงพยาบาล พศ.2555.
กรุงเทพ: โรงพิมพ์ตะวันออก, 2557. หน้า 3.

10. CANCER BIOLOGY

11. • Six essential that dictate malignant growth:
– Self-sufficiency of growth signal
– Insensitivity to growth inhibitory signal
– Evasion of apoptosis
– Potential for limitless replication
– Angiogenesis
– Invasion and metastasis
Hallmarks of Cancer

12. Brunicardi FC et al. Schwartz’s Principles of Surgery. 10th ed. McGraw-Hill Education, 2015. page 280

13. • Oncogenes: proto-oncogene mutation
• Proto-oncogenes: help cells grow. Cells will grow
out of control when mutate and lead to cancer
• Tumor-suppressor genes: normal genes that slow
down cell division, when don't work properly,
cells can grow out of control, which can lead to
cancer

14. Genes Associated with Hereditary Cancer Risk
• Tumor development at a much younger age than
usual
• Presence of bilateral disease
• Presence of multiple primary malignancy
• Presentation of a cancer in the less affect sex
• Clustering of the same cancer type in relatives
• Occurrence of cancer in association with other
conditions such as mental retardation or
pathognomonic skin lesions

15. • Rb1 Gene: retinoblastoma
• P53: Li-Fraumeni syndrome
• BRCA1, BRCA2: breast-ovarian cancer
• APC: Familial Adenomatous Polyposis (FAP)
• p16: hereditary malignant melanoma

16. Chemical Carcinogens
• Tobacco: nasal cancer
• Aflatoxin: HCC
• Coal: lung, skin
• Benzene: ANLL

17. Physical Carcinogens
• Helicobacter pylori: gastric cancer
• Opisthorchis viverrini: cholangiocarcinoma
• Asbestos and silica: lung and mesothelial
cancer

18. Viral Carcinogens
Brunicardi FC et al. Schwartz’s Principles of Surgery. 10th ed. McGraw-Hill Education, 2015. page 295.

19. Cancer Screening

24. Cancer Diagnosis
• Definitive diagnosis of solid tumor is obtained
by biopsy
– Mucosal lesion: by endoscope
– Palpable lesion: excise or punch biopsy
– Non-palpable: ultrasound or CT-guided
– Always orientate the tissue
– Do not contaminate to reduce local recurrence

25. • Fine-Needle Aspiration (FNA)
– Easy and safe
– Only cytology, no information on tissue
architecture
– Fix specimen in 95% alcohol
– Example: thyroid, breast, lymph node
Cancer Diagnosis

26. • Core-needle biopsy
– Safe
– Best with under ultrasound-guided
– Histologic finding
– Disadvantage: sampling error
Cancer Diagnosis

27. • Incisional biopsy
– Large lesion
– Outside
• Excisional biopsy
– Small lesion
– Curative intent with negative tissue margin
Cancer Diagnosis

28. Cancer Staging
• The most widely accepted systems are
American Joint Committee on Cancer (AJCC)
and the International Union Against Cancer
(UICC)
• TNM: tumor, node, metastasis
• Staging system may include prognostic factors
such as tumor size, location, extent, grade, and
dissemination to regional lymph nodes or
distant sites

29. • Patients considered to be high risk for distant
metastasis usually undergo preoperative
staging work-up
– A set of imaging of preferential metastatis
– CXR, U/S upper abdomen, bone scan to rule out
lung, liver, bone metastasis
– Or CT abdomen
Cancer Staging

30. Tumor Markers
• Prognostic marker: molecular marker that
predict disease-free survival
• Predictive marker: predicting response to
certain therapies
– ER, HER2 in breast cancer

31. • Allow early diagnosis
• Limitations:
– Tumor markers levels can be elevated in benign
conditions
– Many are low sensitivities and specificities
– Not specific for certain type of cancer
Tumor Markers

32. • Prostate-Specific Antigen (PSA)
– Elevated in both BPH and prostate cancer
– Normal is below 4 ng/mL
– Use for prostate cancer screening becomes
controversial due to over diagnosis and over
treatment
Tumor Markers

33. • Carcinoembryonic Antigen (CEA)
– Detected in primary colorectal, breast, lung,
ovarian, prostate, liver, pancreatic cancer
– In benign condition: diverticulitis, peptic ulcer,
bronchitis, liver abscess, alcoholic cirrhosis
– “smoker”
– Pre-op elevation of CEA in CRC = poor prognosis
Tumor Markers

34. • Alpha-Fetoprotein (AFP)
– Produced by developing fetus
– Eleveated in HCC and germ cell tumor of ovary
and testicle
– Also in cirrhosis, hepatic necrosis, acute hepatitis,
ataxia, pregnancy
– Sensitivity for detecting HCC is 60%: enough for
screening
Tumor Markers

35. European Association for the Study of the Liver. EASL-EORTC Clinical Practice
Guidelines: Management of hepatocellular carcinoma. Journal of Hepatology 2012
vol.56:908-43.

36. • Cancer Antigen 19-9 (CA19-9)
– Mostly used in cholangiocarcinoma despite low
sensitivity (40-70%) and specificity (50-80%)
with positive predictive value of 16-40%
– Insufficient to screen or monitor colon and
pancreatic cancer
Tumor Markers

37. Multidisciplinary Approach to Cancer
• Surgery is an effective therapy for most solid
tumor
• But patients who die from cancer usually die
from metastatic disease
• To improve survival rates, systemic and
radiation therapy are the key

38. Surgical Management of
Primary Tumor
• The goal is to achieve oncologic cure
• Inoperable disease: primary tumor is not
resectable with negative margin
• Determine the operability by imaging before
surgery: thin-section CT scan
• Appropriate margin depends on type of cancer

39. Surgical Management of
Regional Lymph Node
• Most oncologic operations have been designed
to remove both primary tumor and draining
lymphatic en bloc
• A formal lymphadenectomy is likely to
minimize the risk of regional recurrence
• In breast, colon, and lung cancer, removal
large number of lymph node improves overall
survival rates

40. • Patients with nodal metastases may be offered
adjuvant therapy
• In clinically negative regional LN, lymphatic
mapping technology and sentinel node biopsy
have the role
Surgical Management of
Regional Lymph Node

41. Brunicardi FC et al. Schwartz’s Principles of Surgery. 10th ed. McGraw-Hill Education, 2015. page 305.

42. • The first node to receive drainage from the
tumor site is termed the sentinel node
• Most likely contained metastases
• The practice is designed to avoid morbidity
from lymph node dissection
• Standard of care in breast cancer and
melanoma
Surgical Management of
Regional Lymph Node

43. Surgical Management of
Distant Metastasis
• Depends on number and sites, cancer types,
rate of growth, previous treatment and
response, patient’s age, physical condition, and
desire
• Usually not curable with surgery
• Cure in selected cases with isolated metastases
to the liver, lung, brain

44. • Goal is to resect with negative margin
• In patients with unresectable liver metastases
due to location near intrahepatic blood vessel,
multifocal, or inadequate LFT, alternative
choice is tumor ablation with cryotherapy or
radiofrequency ablation
Surgical Management of
Distant Metastasis

45. Chemotherapy
• Primary modality for patient with distant
metastasis
• Adjuvant therapy: chemotherapy administered
to patients with high risk to distant recurrence
but no evidence
– Goal is to eradicate micrometastatic disease

46. • Principles: destroys cells by first-order kinetics
= a constant percentage of cells is killed, not a
constant number of cells
– 1 kg to 1 g to 1 mg rather being eliminate totally
Chemotherapy

47. • Combination therapy: providing greater
efficacy than single therapy by mechanisms
– Maximum cell kill
– Broader range of coverage of resistant cell lines
– Delays the emergence of drug-resistant cell-lines
Chemotherapy

49. • Toxicity: normal tissue with a high growth
fraction are sensitive to chemotherapeutic
effects:
– Bone marrow
– Oral and intestinal mucosa
– Hair follicles
– Testes and ovaries
Chemotherapy

50. Hormonal Therapy
• Most notably breast and prostate cancer
• Tissue growth under hormonal control
• Examples:
– Surgical ablation: salpingo-oophorectomy
– Androgens: danazol
– Antiandrogens: abiraterone, casodex
– glucocorticoids
– gonadotropin inhibitors

51. • Examples:
– Antiestrogens: tamoxifen, clomifene citrate,
fulvestrant
– Estrogens: primarin
– Progestins: provera
– aromatase inhibitors: letrozole
– somatostatin analogues: octreotide
Hormonal Therapy

52. Targeted Therapy
• Directed at the processes involved in tumor
growth
• Major groups: growth factor receptor
inhibitors, inhibitors of intracellular signal
transduction, cell-cycle inhibitors, apoptosis-
based therapies, and antiangiogenic compound
• Examples: imatinib, trastuzumab,
bevacizumab, lapatinib

53. Immunotherapy
• The aim is to induce or potentiate inherent
antitumor immunity that can destroy cancer
cells
• Example: ipilimumab (cytotoxic T lymphocyte
antigen 4: CTLA-4) on phase 3 study

54. Gene Therapy
• Variety of strategy
• Enhancement of immune responses to cancer
cells
• Replacement of mutated or deleted tumor-
suppressor gene

55. Radiation Therapy
• Results in DNA damage
• The goal of adjuvant radiotherapy is to
decrease local regional recurrence rate
• For inoperable tumor: to make it operable (but
increase risk of wound healing problem)
• For palliation: to reduce symptom

56. • Fractionation = delivery of radiation in divided
doses
• Planning: Conventional Fractionation
– 1.8 – 2 Gy/day
– 5 days each week
– For 3 – 7 weeks
Radiation Therapy

57. • Mainly use in
– Cervial cancer
– Prostate cancer
– Lung cancer
– Esophageal cancer
Radiation Therapy

58. Radiation Therapy

60. Response criteria: target lesion
• Complete Response (CR)
– Disappearance all target lesion
– Any pathological LN have reduction < 10mm
• Partial Response (PR)
– At least 30% decrease in sum of diameters of
target lesions

61. • Progressive Disease (PD)
– At least 20% progression
– New lesion
• Stable Disease (SD)
Response criteria: target lesion

62. • Target lesion: maximum 5 measurable lesions
(maximum of 2 lesions per organ)
• Non-target lesion: all other lesion including
pathological LN
• Baseline sum diameter: diameter of target
lesions that calculated as baseline

63. • Measurable lesion:
– 10 mm by CT
– 10 mm by clinical exam
– 20 mm by CXR
– For malignant LN, 15 mm will be measurable
• Non-measurable lesion
– All other lesion including small lesion
– Pathological LN at least 10 mm < 15 mm

64. References
Brunicardi FC et al. Schwartz’s Principles of Surgery. 10th ed. McGraw-Hill Education, 2015.
Townsend CM et al. Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical
Practice. 19th ed. Philadelphia: Elsevier Saunders, 2012.
European Association for the Study of the Liver. EASL-EORTC Clinical Practice Guidelines:
Management of hepatocellular carcinoma. Journal of Hepatology 2012 vol.56:908-43.
Khan SA et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut
2012; 61:1657-69.
Eisenhauer EA et al. New response evaluation criteria in solid tumours: Revised RECIST
guideline (version 1.1). European Journal of Cancer 45 (2009) 228-47.
www.cancer.org
http://www.nci.go.th/th/index1.html

65. สมาคมศัลยแพทย์ระบบปัสสาวะแห่งประเทศไทยในพระบรมราชูปถัมภ์. ตารามะเร็งต่อม
ลูกหมาก. กรุงเทพ: บียอนด์ เอนเตอร์ไพรซ์, 2556.
สถาบันมะเร็งแห่งชาติ กรมการแพทย์ กระทรวงสาธารณสุข. ทะเบียนมะเร็งระดับโรงพยาบาล
พศ.2555. กรุงเทพ: โรงพิมพ์ตะวันออก, 2557.
เอกสารประกอบการเรียนการสอน basic science 2558
References