Oncology PDF

## ONCOLOGY - m/c form of tumor worldwide - **SKIN CANCER** - most imp regulator of apoptosis - **p53 TSG** - Normal cells stop proliferating & enter a quiescent stage - **Go** - Cells in Go and G2 are receptive to growth signals. - **Epidermal growth factor (EGFR)**: overexpressed receptor in **in...

## ONCOLOGY - m/c form of tumor worldwide - **SKIN CANCER** - most imp regulator of apoptosis - **p53 TSG** - Normal cells stop proliferating & enter a quiescent stage - **Go** - Cells in Go and G2 are receptive to growth signals. - **Epidermal growth factor (EGFR)**: overexpressed receptor in **ing & GIT cancers** - **HER2/neu receptor**: **Breast cancer** - **Telemerase** - adds nucleotides to telomeres - allowing continued cell division - absent in normal cells - over-expressed in **cancer cells** - **Cadhesin-1 (CDH1)** - ↑ expression is recognized as an antagonist of invasion & mets. - Loss of CAH-1: tumors become invasive - The ability to escape from immunity is a hallmark of CANCER. - Tobacco - major factor in the etiology of 30%. Cancers - m/c solid organ malignancies - **lung, breast** ## Environmental factors predisposing to cancer | Factor | Associated Cancer | | ----------------------------- | ----------------------------------- | | Bladder cancer | Dye & rubber manufacturing (aromatic amines) | | Asbestos/mining/construction | lung cancer | | PVC | Mesothelioma | | Chemotherapy | AML | | Inhaled smoke | lung & Bladder CA | | EBV | Burkitt's lymphoma + nasopharyngeal CA | | HPV | cervical HCC | | Hep B, C | Cholangiocarcinoma | | Liver fluke (Opisthorchis sinensis) | SCC of bladder | | Schistosoma | - | | Low roughage/high fat | colonic CA | | High nitrosamine intake | gastric CA | ## CT exposure - Occupational exposure (Beryllium and strontium mining) - Cholangiocarcinoma - Therapeutic radiotherapy - lung cancer - - Medullary thyroid cancer - - Sarcoma - Diethylstilbestrol oestrogens - vaginal, endometrial, Breast cancer ## Genes | Gene | Associated Gene/Mutation | | ---------- | ----------------------------------- | | MEN-1 | MEN I gene | | MEN-2 | RET | | Papillary | MET | | Renal cell CA | - | | Peutz Jegher | STK 11 | | Prostate CA | HPC 1 | ## INVESTIGATIONS - Overall fitness of apt is assessed by the Eastern Cooperative Oncology group (ECOG) performance scale: | ECOG Scale | Description | | ----------- | -------------------------------------------------------------------------------- | | 0 | Fully active, no restrictions in carrying out usual activities | | 1 | Fully active but only with aid of analgesics Restricted strenuous activity, carries out light work/sedentary occupation | | 2 | Ambulatory & able to take care of himself but unable to work (75% of waking hrs) | | 3 | Limited self care, confined to bed/wheel chair (75% of waking hours) | | 4 | Completely disabled, can't carry out any self care. | ## TNM staging (UICC) for all cancers - Colon cancer uses Dukes system instead of UICC. ## HISTOLOGV - Psammoma bodies - the mucin - Ovarian CA - -ve mucin - thyroid CA - High levels of HER2 indicates sensitivity towards Tx by trastuzumab (Herceptin). ## RADIOLOGY - U/S - breast, liver - U/S endoscopy - GIT & pancreatic cancers - CT - thorax & ab domen - MRI - pelvis, staging rectal, cervical & prostate CA - PET scan - severity & spread of tumors ## Common tumor markers 1. AFP - testicular teentoma - germ cell tumor of ovary 2. Calcitonin - Medullary cell CA of thyroid 3. CA-125 - Ovarian epithelial cell tumor (GIT, lung, breast CA) 4. CA-19.9 - pancreatic cancer - mucinous cancer of ovary - other - Gastric, colon 5. CEA - Colorectal cancer wd liver mets 6. HCG - Chorio CA (100%) - Hydatiform mole (98%) - germ cell tumors 7. PSA - prostate CA 8. Thyroglobulin - pap: Lacy & follicular thyroid CA 9. PLAP - Ovarian dysgerminoma - Seminoma - SCC of lung - ADH (hypona) - ACTH (Cushing's) - Lambert Eaton Syndrome - FGF 23 (Hypophosphatemic osteomalacia) - Mesenchymal tumors - Insulinoma - Insulin ## PTHP - Non SCC of lung. - Uterine fibroids, kidney, hepatoma - around 50% of cancers occur in the 15% of the population aged over 65 yrs. ## EMERGENCY COMPLICATIONS OF CANCER ### SPINAL CORD COMPRESSION - Confirm Dx wd urgent MRI - High dose steroids - Dexamethasone IV stat - Dexa twice daily orally - Ensure adequate analgesia - (Neurosurgical decompression/radiotherapy) | Clinical feature | Spinal Cord | Conus medullaris | Cauda Equina | | ----------------------- | ------------ | ---------------- | ------------- | | Weakness | Symmetrical & profound | Symmetrical & variable | Asymmetrical | | Reflexes | ↑ or absent wd extensor plantar reflex | ↑ knee reflex, ankle reflex, extensor plantar reflex | ↑ knee & ankle reflexes, flexor plantar reflex | | Sensory loss | Symmetrical, sensory level | Symmetrical, saddle distribution | Asymmetrical, radicular pattern, spared | | Sphincters progression | Late loss, rapid | Early loss , variable | - | ## SUPERIOR VENA CAVA OBSTRUCTION - Occurs due to extrinsic compression or intravascular blockage. | Cause | Associated Condition | | ------------------------ | ------------------------------------- | | Extrinsic causes | Lung CA, Lymphoma, metastatic tumors | | Intravascular causes | central catheter, thrombophilia sec. to leukemia, tumor | ### S/S - Edema of arms + face - Distended neck and arm veins. - Dusky skin coloration over the chest, arms & face. - Collaterals develop in a few weeks & flow of blood in the collaterals helps to establish a diagnosis. - Headache sec to cerebral edema (aggravated by bending forward, stooping or lying down) - Dyspnea (63%) - m/c symptom - Facial swelling & head swellness - Physical findings - Venous distention of Neck - ↓ facial edema - ↓ chest wall cyanosis - ↓ plethora of face ### Dx - Investigation of choice: - CT of thorax (distinguishes b/w intravascular & extrinsic causes) - Biopsy of tumor - Tx: - Mediastinal radiotherapy - stenting (if chemo or radio-resistant) ## HYPERCALCEMIA - m/c Metabolic disorder in pts wd CANCER. - Highest incidence: Myeloma and breast cancers due to overproduction of PTHrP. - 8/8 - drowsiness, confusion, N/V, constipation, polyuria, polydipsia & dehydration. - Hypercalcemia is a sign of tumor progression. ### Dx - Serum total Ca and adjusting for albumin ### Tx - IV 0.9% NS - (2-4 L/day) - IV bisphosphosphonates (Zoledronic acid or pamidronate) - IM/SC Calcitonin for the first 24-48h in life threatening hypercalcemia ## NEUTROPENIC FEVER: - Usually sec. to chemotherapy but may occur sec. to radiotherapy as well. ### Def - Pyrexia of 38°C for over 1h in a pt wd Neutrophil count <1.0x10^9/L ### Emergency b/c if left untreated - Septicemia with a high mortality rate ### S/S - High grade fever - Generally in-well patient - Hypotension (adverse prognostic feature) - leads to organ failure ### Dx - Infection screening (BC, UC, CXR, throat swabs etc) ### Tx - Start high dose IV Antibiotics - If no response after 36-48 hrs - give amphotericin B or voriconazole (to cover fungal infection) ## METASTATIC DISEASE - Metastatic Dx is the major cause of death in cancer pts & the principal cause of morbidity. - Tx is usually palliative. ### BRAIN METS - m/c arise from the LUNG. - S/S: - headaches (50%) - focal neurological deficits - cognitive dysfunction - seizures - Dx: - CT or contrast enhanced MRI - Tx: - High-dose steroids (for edema) - anti-convulsants - whole brain radio & chemo ### LUNG METS - Cause from Breast CA, colon cancer, tumors of HN. - Lesion found on CXR or CT - >2 nodules - assumed to be mets. - Tx: - Surgery for solitary lesion - Radio/chemo for the rest. ### LIVER METS - Colorectal CA, oailar melanoma, neuro endocrine tumors. - S/S: - RUP pain, jaundice, deranged LFTS, abnormality on imaging. ### BONE METS - 3rd m/c organ involved by Mets after lung & liver. - Arise from myeloma, Breast, prostate CA. - S/S: - pain, pathologic fractures, SC compression - Most pathological fractures occur in metastatic Breast CA (53%), followed by Kidney (11%), Lung (8%), Lymphome, Thyroid & prostate (3%). - (most sensitive) ### Dx - Isotope Bone Scan - false - ve - Multiple Myeloma (due to osteoblast suppression) - false + ve - Healing Bone - So plain X-rays are preferred (1st line) ### Tx - IV bisphosphonates (pamidronate, zoledronic acid or ibandronate) - HRT for Breast/prostate CA. - Radiotherapy ## MALIGNANT PLEURAL EFFUSION - m/c complication - 40% of all pleural effusion are due to malignancy. - m/c causes - Breast & lung CA. ### Dx - Pleural Aspirate (1.5L max) - Aspirate may show malignant cells (Malignant effusion are blood stained, exudative with & raised LDH ratio >0.6, LDH: serum protein >0.5) ### Tx - Palliative aspiration alone may relieve symptoms. - Pleurodesis, pleurectomy & pleuroperitoneal shunt. - Reaurent PE - curative - palliative ## THERAPEUTICS IN ONCOLOGY 1. Palliative chemo - m/c form of treatment used to Tx mets. - Goal is symptomatic relief with better quality of life. 2. Adjuvant chemo - To cyto-reduce the tumor bulk & remove macroscopic disease. - Give chemo to reduce microscopic disease. 3. Neoadjuvant chemo (pri medical therapy) - Chemo is given prior to a cyto-reductive procedure. - ↓ surgery requirement. 4. Chemoprevention - Use of pharmacological agents to prevent cancer developing in high-risk patients. ## SURGICAL TREATMENT - m/c curative management of most solid cancers is "surgical excision." - Chemo is given via IV injection every 3-4 weeks. - Myelosuppression is common to all cytotoxics - Neutropenia risk can be ↓ by giving granulocyte-colony stimulating factor (G-CSF) along with chemo. ## TYPES OF RADIOTHERAPIES - Teletherapy: application from a distance by a linear accelerator. - Brachytherapy: Direct application of a radioactive source onto or into a tumor. - dis - or high-dose localized radiotherapy for localized cancers of H&N, cervix & endometrium. - IV Radioisotope - 131 iodine: thyroid cancer - 89 strontium: bone mets from prostate cancer. - Majority of treatments are delivered by linear accelerations. - Normal tissues of CNS, SI & lung are highly sensitive to radiotherapy. - Late side effects develop bwks after therapy. - Hormone therapy - used for Breast & prostate cancers. ## Biological therapies 1. Gefitinib/erlotinib: inhibit epidermal GF 2. Imatinib: inhibit BCR-ABL gene product tyrosine kinase (CML Tx) 3. Bevacizumab: monoclonal AB that inhibits VEGF-A. 4. Trastuzumab (herceptin): targets HER2 receptor (Breast CA) ## BREAST CANCER - m/c histological subtype - DCIS (70%) - Distant mets- Bone (70%), Lung (60%), Liver (55%), pleura, adrenals, skin & brain. ### Dx - Best initial = FNA - Core needle biopsy - ERtve, PRtve, HER2tve cancer - Open biopsy - most accurate Dx test (diff b/w solid & cystic mass) - UIS < 35 yrs (diff b/w solid & cystic mass) - Mammography > 35 yrs (usually 50) - -ve sentinel node biopsy: no need for axillary node dissection. ### Tx - Surgery is the mainstay of Tx - ER and AR the cancer - tamoxifen/raloxifen - (aromatase inhibitors) - anastrazole, letrozole, exemestane - HER2/Neu tve - Trastuzumab - Adjuvant chemo - ER-ve tumor > 1cm, axillary L.N involved ## METASTATIC DX - Radiotherapy (palliative) - Endocrine therapy with aromatase inhibitors. ## OVARIAN CANCER - m/c gynaecological tumor (and m/c - cervical) - m/c type - Epithelial - S/S - age > 50, vague abdominal discomfort & low back pain, bloating, ↑ girth, altered bowel habits, wt loss. - peritoneal deposits - omental cake, Sister Mary Joseph nodules. - ↑ risk: - BRCA 1 & BRCA 2 - HNPCC - Nulliparity - ↑ Age - Dx: - U/S or CT - CA-125 tumor marker (check for relapse) - Tx: - surgery + carboplatin + paclitaxel. (BSO + total hysterectomy + omentectomy) - Bevacizumab - aggressive tumors. ## TESTICULAR CANCER - Painless lump in the scrotum that doesn't transilluminate - Hx of cryptorchidism, cryptorchidism. ### Dx: - Needly biopsy never done - Remove the whole testide with inguinal orchiectomy. - + HCG ### Tx: - Orchiectomy + Radication (local Dx) - Orchiectomy + chemo (widespread Dx)