Principles of Surgical Oncology Flashcards
What are the 5 principles of surgical oncology?
- Tumor biology
- Goals & principles in cancer surgery
- Principles of systemic therapy & radiation therapy
- Cancer treatment strategies under multisciplinary approach
- Advances in oncology
What should u take note of in tumor growth 7 occurence of metasis?
- knowing abt the behavior of the tumor: how fast it grows, how quick it metastasizes
- pattern & distribution of metastiasis
- tumor factors affecting outcomes/prognosis
- margins of resection
What are the phase of cell cycle?
Interphase: G1 -> S -> G2 -> M
What is the deciding factor for a ell to enter G0 phase?
Presence or absence of growth factors or nutrients
If present -> G1
If absent -> G0 -> can be reversible/irreversible
What are the 2 mechanisms of Cell Cycle control?
- Checkpoint control
- Cyclins
What are critical events in Checkpoint control?
DNA replication
Chromosome segregation
WHat are the differnt checkpoints in checkpoint control?
G1/S (R pont) CHeckpoint = primary determining factor for cell division to take place
G2 Checkpoint = represents commmitment for starting mitosis, DNA replicated correctly
M/Spindle checkpoint = ensures all chromosomes are attached to the spindle in preparation of mitosis
What happens if there are problems in the # of growht factors in G1, damge in replicated DNA in G2 or problem with spindl eformation in M phase?
Cell cycle proceeds —> uncontrolled cellular replication —> cancer
What are proteins tha tcontrol the progression of cells through the cell cycle?
Cyclins
What enzyme activates Cyclins?
Cycline-dependent kinase
What is a central part of all phases of the maintenance of cell cycle?
Regulation of Cyclin/CDK activity?
What can happen if Cyclin/CDK activity iscompromised?
Malignant transformation of cells
What are the diff factors assoc with Carcinogenesis?
Genes
Carcinogens
Cancer cells
What are the 2 classes of cancer genes?
Oncogenes = stimualtes growth of cells; positive growth regulators
Tumor suppressor genes = blocks G1/S phase; promotes apoptosis; negative growth regulators; loss of function mutation of proteins
What are ocongenes high in lung, pancreas, colon, thryoid, & breast?
Breast cancer = HER2 NEU
Lungs, pancreas, colon, & thyroid cancers = Ras
What hereditary cancer is associated with APC gene?
Familial adenomatous polyposis
What hereditary cancer is associated with BMPRIA gene?
Juvenile polyposis coli
What hereditary cancer is associated with BRCA1/BRCA2 gene?
Breast/Ovarian syndorme
What hereditary cancer is associated with hMLHI, hMSH2, hMSH6, hPMSI, hPMS2 gene?
Hereditary nonpolyposis colorectal cancer
What are the different oncogenic viruses?
EBV = Gastric cancer, lymphoma
HPV = Cervical cancer, vulvar cancer
Hepa B, C = liver cancer
HIV = Kaposi sarcoma
What are diff oncogenic causes of chemicals?
Aflatoxin = Liver cancer
Arsenic = Skin cancer
Estrogen replacement therapy & Tamoxifen = Endometrial cancer
Tobacco = Oral cavity cancer, lung cancer, pancreatic cancer, esophageal cancer
Benzidine = urinary bladder cancer
What are different carcinogenc caused by chronic irritation?
Ulcerative colitis = Colon cancer
GERD = Esophageal cancer
Marjolin’s ulcer = Squamou CC, Basal cell carcinoma of the skin
What are hallmarks of cancer cells?
Sustained proliferative signaling
Insensitive to growth suppressors
Resist cell death (apoptosis)
Replicative immortality
Induces angiogenesis
Evades immune response
Creates tumor microenvironment
Invasion & Metastasis
What are the 5 most common cancers in PH?
Breast cancer
Lung cancer
Colorectal cancer
Liver cancer
Prostate cancer
What are the most prevalent cancers in Males?
Lung
Colorectum
Prostate
Liver
Leukemia
What er the most prevalent cancers in Females?
Breast
Uterus/Cervix
Colorectum
Lungs
Ovary
What type of cancer has the highest incidence & mortality rate? Followed by?
Breast
- Prostate
- Lungs
What type of cancer is easily screened & should be screened early because of its aggressive behavior & high mortality rate?
Breast & prostate cancers
What is the scheduled screening test for breast cancer?
45 y/o & above
Annually
Mammography
What is the scheduled screening test for lung cancer?
50-80yo
Smoker with 20 pack yrs or have quit smoking for the last 15 yrs
Low dose chest
CT scan
What is the scheduled screening test for Cervical cancer?
25yo
Every 5 yrs until 65 yo
Pap smear
HPV test
What is the scheduled screening test for colorectal cancer?
45 yo
Annually until 75 yo for ave risk
Highly sensitive fecal immunochemical test
GFOBT
What are other scheduled screening for colorectal cancer?
Every 10 yrs = Colonoscopy
Every 5 yrs = Flexible sigmoidoscopy
At what age should one be screened for prostate cancer?
50 yo = ave risk; expected to live 10 yrs
45 yo = high risk
40 yo = even higher risk
screening every 1-2 yrs = Prostate Specific Antigen
50yo & > = DRE
Tumor growth is best described & tracked by what chart?
Gompterzian curve
- if tumor is small in size -> growth rate is close to 100% -> sensitive to tx/treatable
What happens to tumors that decrease in growth rate bcos of lack of nutrients and blood supply?
Bcomes more aggressive => cancer cells are in cell cycle phase -> easily metastasize/invade other surrounding structures -> very lethal
What is the expression of tumor growth?
Volume doubling time
Whta is the range of doubling time in breast, lugns, melanoma, & metastatic melanoma?
MM - 64 days
Breast = 130 days
Melanoma - 140 days
Lungs = 160 days
In clinical impression of breat CA, what do u do if a px comes to u w/ sonograpihc findings of a 1cm nodule, not highly suspicious ofmalignancy?
- Repeat ultrasound after 3-4 mons
- If size increases to 1.5 - 2cm, it is malignant and should undergo tissue biopsy
In clinical impression of lung CA, what should u do if a px comes to u w/ CXR of 1cm ndule on apex, no history of pulmonary TB?
- Request for another imaging after 3-4 mons
- If there’s increase in size -> suspicious for malignancy
What are the main diff betw slow growing & fast growing tumors?
Slow growing tumors
- curable with surgery alone
- Appendiceal Carcinoma with low malignant potential: Pseudomyxoma peritoei
- Well-differentiated thyroid carcinoma: Papillary thyroid carcinoma, Follicular thyroid carcinoma
Fast growing tumors
- likely metastatic
- curable with multimodal tx
- surgery + chemotherapy (+/- radiation)
What are examples of fast growting tumors?
Pancreatic adenocarcinoma
Gastric adenocarcinoma
Esophageal adenocarcinoma
Esophageal carcinoma
What is TUmoriogenesis?
Oncogene mutation -> cells likely to divide more -> Dysplasia stage -> overgrowing cells change orig form & behavior -> In situ cancer -> cells grow rapidly, lost their tissue identity, & grow w/o regulation -> malignant tumor -> invade neigboring areas & blood circulation system -> autophagy
What are the 2 roles of tumorigenesis?
Tumor-suppressing role during the early stage
Cancer promiting role during late stage
What occurs in early metastasis?
Primary organ: GIT, oral cavity
Histo: Adenocarcinoma
Diff: Poorly-differnetiated
Depth of penetration: Submucosal, higher rate of metastasis
Genetic profile: Her2+, Er-
Size: >2cm
Lymph node metastasis: Present
What are the occurence of late metastasis?
Primary organ: thyroid, breast
Hist: Neuroendocrine
Differentiation: well-differentiated
Depth of penetration: Mucosal
Genetic profile: Her 2-, Er +
Size: <2cm
Lymph node metastasis: Absent
What are the differnt patterns & distribution orgagns of metastasis?
Lymph nodes
Blood
Coelomic
What are the route & pattern of Metastasis?
Lungs = Mediastinal LN, + blood, - Coelemic
Breat = Axillary LN, + blood, - Coelemic
Thyroid = Cervical LN, + blood, - Coelemic
Colon/Rectal stomach = Mesenteric/Pelvic perigastric LN, + Blood, + Coelomic
Sarcoma = Rarely, + Blood, - Coelomic
What is the path of metastasis?
Carcinoma first metastasizes to the lymphatics
Sarcoma invades bloodstream
Does sarcoma produce transcoelomic metastasis?
Rarely EXCEPT for Intraperitoneal sarcomas
What happens if abdominal cavity is ruptured in Uterine leiomyosarcoma?
Present with peritoneal carcinomatosis
What are the different patterns of solid organ mestasis?
Site of metastasis: brain
Primary tumors: 1. Lung, 2. Breast, 3. Melanoma, 4. Renal cell, 5. Colorectal
What is the pattern of solid organ metastasis of the lungs?
- Renal cell
- Colorectal
- Melanoma
- Breast
- Sarcoma
What pattern of solid organ metastasis of the liver?
- Colorectal
- Pancreatic
- Breast
- Lung
- Stomach
What is the pattern of organ metastasis of the Bone?
- Breast
- Lung
- Prostate
- Renal cell
- Colorectal
Where does colroectal carcinoma metastasize?
- Lungs
- Lungs
Where does Periphera/Extermities Sarcoma metastasize?
Lung
Where does Retro/Intraperioneal Sarcoma metastasize?
Liver
What are the significance of lymph node metastasis & pattern of spread?
Indicator systemic therapy +/- radiation therapy
Into what regional lymph node does Stomah cancer drain to?
Perigastric LN
What regional lymph node does rectal cancer drain to?
Mesorectal lymph nodes
What regional lymph node does colon cancer drain to?
Mesenteric lymph nodes along vascular pedicle
What are clinical implications of metastatic tumor?
Tumor of breast = remove breast + axillary LN
Gastric CA = remove stomach + perigastric lympph node
What are factors that INC incidence of lNC metastasis?
- Size of primary tumor
- Depth of invasion of the primary tumor
- Histo features
What are the sizes of breast cancer & Papillary thyroid cancer when incidence of LN metastasis?
Breast cancer = >2cm, >15% in the axilla
Papillary thyroid cancer = >5mm, 15-65% in the cervical LN
What is the depth of invasion of the primary tumor that INC incidence of LN metastases?
- 20% submucosal invasion in the GIT
- > 15% tongue SCC >5mm
What are histo features seen in INC of LN metastasis?
- Epithelial-adenocarcinoma of GIT = high chance of LN metastasis
- Mesenchymal tissue-sarcoma of the soft tissue = low chance, not expected LN metastasis
What lymph node metasis influences prognosis of cancer?
Survival
Local recurrence
Least impact on the tumors of the thyroid
What are the influence on survival & recurrence of LN metasis?
Decreased Survival rates
YES = breast, colon, gynecologic, sarcoma, oral cavity squamous CC
NO = thyroid
Increae loco-regional recurrence
YES = breast, colon, gynecologic, sarcoma, thyroid, oral cavity squamous cell carcinoma
What is the route & pattern of LN Metastasis?
- Invasive ductal carcinoma of the breast
A. Level 1, 2, 3 axillary LN -> intercostal -> mediastinal & supra-clavicular LN - Squamous CC of the anterior tongue
A. Level 1, 2, 3 cervical LN initially -> level 4-6 of cervical LN of the neck
What are clinical implications of LN metastasis?
Prophylactic neck dissection or Supraomohyoid neck dissection
What is TNM?
Staging of metastasis
Size of the primary Tumor
Number of Lymph node metastasis
Site of distant Metastasis
What is stage 0 of cancer?
Carcinoma in situ (CIS)
Abnormal cells are present but have not spread to neaby tissue
What is the tumor marker for colorectal & breast cancer?
CEA
What tumor marker is fpr Hepatocellular carcinoma?
AFP
What tumor marker is for pancreatic cancer?
CA 19-9
What are the differnet ways to do a tissue biopsy?
Fine needle aspiration biopsy
Core needle biopsy
Incision biopsy
Excision biopsy
What type of tissue biopsy uses a thin, hollow needle & used foor palpable superficial tumors like enlarge lymph nodes, breast lumps, and thyroid tumors?
Fine needle aspiration biopsy/Cytology
What are advantages & disadvantages of fine need biopsy?
Advantages:
- diagnose benign vs malignant tumor
- safe, conventient & simple
- excellent for thyroid mass/nodule
Disadvantages
- inadequate to diff in-situ vs invasive (breast tumor), sarcoma vs carcinoma or lymphoma vs TB
- spx not enough for immunostaining
What type of core needle biopsy makes use of a large-bore needle that is best used if histologic characteristics are consistent with the clinical scenario?
Core needle biopsy
What are advantages of Core needle biopsy?
- Provides a degree of architectural iinformation = increased diagnostic yield
- used for genetic tests (breast cancer)
- immunohistochemical staning can be performed
What are disadvantages of core needle biopsy?
- cannot be used in tissues near a major BV
- longer fixation & processing time
- more expensive
What type of biopsy is used for indeterminate soft tissue masses as a more reliable, accurate, and confirmatory means of determining malignnacy, establishing the exact diagnosis?
Open biopsy
What are the 2 types of open biopsy?
Incision biopsy
Excision biopsy
In what case do u use incision biopsy?
For difficult to remove lesions due to size or location
What type of open biopsy is used for complete removal of the mass with a margin of normal tissue?
Excision biopsy
From open biopsy, core needle biopsy, and fine needle aspiration biopsy, which one is the most accurate among all the biopsy procedures?
Open biopsy
In what cases do we give palliative surgery?
Px with unresectable tumors, incurable disease/metastatic but longevity and quality of life can still be improved
Address the pain, bleeding, or GIT obstruction
What is a prophylactic surgery?
Risk reducing surgery = to prevent future cancer from developing
What is a supportive surgery? Examples?
Performed for nutritional access or medical treatment
Port-A-Cath = implanted below the skin
Feeding tube (Jejunostomy/Gastrostomy) = px who can no longer eat through their mouth
How do u assess the completeness of the primary tumor and draining of lymph nodes at risk of metastasis?
Margins of resection
Pattern of lymph node invovlement
In what cases do u perform oncologic resection?
Non-metastatic tumors (stage 1-3)
What are the goals of oncologic resection?
- Remove tumor w/ adequate margins of normal tissue & ensure no gross and microscopic cancer cells will be left behind
R0 = no microscopic tumor at the margins of resection
R1 = positive microscopic tumor at the margins of resection
R2 = positive gross residual tumors
- Primary tumor should be removed in continuity with regional lymph node
what is lymph nodes are not at risk for metastasis, what is the goal of the surgery then?
Complete resection of the primary tumor with negative margins of resection only
What happens if the primary tumor invades or seemed contiguous with another organ or tissue?
Do en bloc resection for the primary tumor (not piecemeal) to avoid spilage of cancer cells
What is done in en block resection?
Remove part of the organ contiguous/involved by the tumor to achieve clear margins of resection of atleast 1cm -> negative surgical margin = no cancer cells at the resected margins (surgical gold std)
What is the distance of Squamous/Adenocarcinoma Esophagus, Gastric adenoma, Colon adenocarcinoma, Rectal adenocarcinoma from the edge of tumor?
Squamous/Adenocarcinoma Esopagus:
- Proximal = >10cm
- Distal = >5cm
- Circumferential radial margin = >1mm
Gastric adenocarcinoma
- Proximal = >5cm
- Distal = >5cm
Colon adenocarcinoma
- corresponds to the vascular pedicle supplying of the colon
- 8-10cm
What is the distance of rectal adenocarcinoma, invasive ductal carcinoma of the breast, non-melanoma skin tumor <2cm, oral cavity, sarcoma from the edge of tumor?
Rectal adenocarcinoma:
- Proximal = >5cm
- Distal = at least 1cm
- Circumferential radial margin should be NEGATIVE for tumor
Invasive ductal carcinoma of the breast
- if breast conserving surgery = atleast 2mm or NEGATIVE tumor in ink margin
Non-Melanoma Skin tumor <2cm: <5mm
Oral cavity: >1cm
Sarcoma: >5cm
What are the characteristics of basal cell carcinoma of the skin?
- marked the edge of tumor w/ at least >4mm margin
- wide excision with atleast 4mm margin in a px with basal cell carcinoma
- wide excision wtih atleast 4mm margin in a px with basal cell carcinoma
What are descriptions of breat cancer curative surgery?
- curative radical mastectomy with axillary LN dissection in a px with breast cancer with chest wall invasion non-responsive to neoadjuvant therapy
- the margins of resection were negative
- radical mastectomy with axillary LN dissection
What are descriptions of of Liposarcoma of the thigh in curative surgery?
- stage 2 liposarcoma of anterolateral thigh
- performed a wide excision or muscle group resection with surgical margins of atleast 5cm
- wide excision of tumor in a px with liposarcoma
What is cytoreductive surgery?
Surgical removal of gross tumors in the metastatic setting
Cancers of the appendix w/ low malignant potential, ovarian cancers, & limited colorectal liver metastasis
What is done in cytoreductive surgeryin px with Solitary colorectal liver metastasis?
Performed a ressection of the primary tumor together with the metastatic tumor to the liver
What are the goals of chemotherapy?
- To kill cancer cells by interfering with its cell cycle with serious damage to normal cells
- Improve chances of cure/longer survival
- Lessen dose of each drug
- Allow normal cells to recover every 14-21 days
what are the 3 types of systemic chemotherapy?
Chemotherapy
Targeted therapy
Immunotherapy
What are type of cancer is chemotherapy effetive or ineffective?
Effective: Lymphoma, Colore adeniCA, Breast CA
Ineffective: Sarcoma, thyroid cancer, GI stroma tumor
What drug classes target G1?
Hormonal drugs = Tamoxifen
Antineoplastic enzymes = Asparaginase, Pegaspargase
What drug classes target S phase?
Topoisomerase-1 inhibitors = Tropotecan, Irinotectan
Antimetabolites:
- Folate Analogs; Methortraxate
- Purine analogs: Mercaptopurine, Thioguanine, Pentostatin
- Pyrmidine analogs: Fluorouracil, Cytarabine
Hydroxyurea
What drug classes target G2 phase?
Epidophyllotoxin derivatives: Etoposide, Teniposide
Taxanes: Docetaxel, Paclitaxel
Bleomycin
What drug class targets M phase?
Vinca alkaloids: Vinblastine, Vincristine, Vinorelbine
Taxane: Docetaxel, Paclitaxel
What is the newest form of cytotoxic therapy where it blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis & tumor growth?
Targeted therapy
What should be done in targeted therapy?
Must test first for the specific gene of that particular tumor wherein the drug will be effective
What is the purpose of immunotherapy?
Blocks the protein molecule released by the tumor
Lung cancer: positive for programmed death lignad 1 blocked by Pemproluzimab
What is radiation therapy?
Local therapeutic effects
Used if there is a risk for local reccurrence despite oncologic resection
What are factors that affect radiosensitivity?
Oxygen tension = prolong 1/2 lfie of free radicals
Drugs that improve sensntivity to radiation = 5-Fluorouracil & Doxorubicin
What are tx strategies in cancer?
Neoadjuvant therapy = prior to curative resection
Adjuvant therapy = after curative resection
What is Genomics?
Determines the exact gene sequence of a particular tumor
What are the targets specific molecules in cancers?
- Epidermal growth factor receptor & Lung Cancer
- Breast cancer
- Colon cancer
What are predictive malignancy-risk gene signature?
Developed to stratify px with possible malignancies who would benefit from systemic chemotherapy
What is Proteomics?
Proteins that are produced or encoded by the mutated genetic dequence in a prticular tumor
What are local tx modalities for tumor control in stage 4 or unresectable tumor?
Radio frequency ablation
Microwave ablation
Selective intra-arterial radiation therapy
What tx for stage 4 tumor is heat-dependent & uses a needle with a tip generating excessive heat to ablate the tumros?
Microwave ablation
What tx for stage 4 tumor introduces radioactive mat to specific cannulated blood supply of tumros to control tumor growth & change of rupture/bleeding in the liver?
Selective intra-arterial radiation therapyh
