Clinical Oncology Flashcards

Question

CA breast common metastasis

Answer 1

Lung, bone, liver, brain

Answer 2

- Clinical assessment —> history + PE - Radiological assessment —> Mammogram (craniocaudal, mediolateral), USG breast (performed together with mammogram, assess axillary LN), ductogram (if have nipple discharge), MRI breast (if previous -ve) - Pathological assessment —> core needle biopsy (performed if BIRADS 4+), FNAC (preferred if low risk, like non-palpable mass or equivocal MMG or simple cyst), excisional biopsy (when core biopsy reveals suspicion lesion but not diagnostic)

Answer 3

• If found on core biopsy: excisional biopsy MUST be performed to rule out malignancy • malignancies contained within basement membrane 1. Ductal carcinoma in situ - usually univocal - mammogram: microcalcifications - precursor to invasive ductal carcinoma of the same breast - higher risk to become malignant - Mx: —> BCS +/- RT (first-line) —> Masetomy + SLNB —> Adjuvant: tamoxifen/AI if ER/PR+ 2. Lobular carcinoma in situ (LCIS) - usually multifocal and multicentic - Precursor and marker of bilateral invasive carcinoma (ductal/ lobular) - Mx: —> Classical LCIS: close observation Non-classical LCIS (pleomorphic): more aggressive à surgical excision

Answer 4

Epidemiology • Incidence in female: 1st; mortality: 3rd • Median age 55 (younger than global data) • Lifetime risk 1: 16 Classification • Invasive ductal carcinoma (76%): urther subclassified into tubular, mucinous (good prognosis), metaplastic, inflammatory (poor prognosis) • Invasive lobular carcinoma (8%): E-cadherin mutation • Others: ductal/lobular (7%), colloid (mucinous) (2.4%), tubular (1.5%), medullary (1.2%), papillary (1%) Clinical features • Breast mass: hard, irregular, fixed, non-tender, mostly at upper outer quadrant • Nipple discharge: increased risk if unilateral, single duct, bloody • Special types: o Paget's disease of nipple: invasion of nipple-areolar complex; unilateral nipple eczema + nipple discharge • Ix: triple assessment, nipple biopsy x Paget cells o Inflammatory breast cancer (T4d): invasion of local lymphatic ducts; painful swollen breast with cutaneous edema involving at least 1/3 of breast (peau d'orange) • Metastasis: bone, liver, lung, brain Risk factors • Unopposed oestrogen: obesity, early menarche, late menopause, nulliparous, no breastfeeding, COC/ HRT • Lifestyle: smoking, alcohol • FHx in 1st deg relative (if young) • Benign breast diseases (refer to table) o Epithelial hyperplasia: atypical ductal / lobular hyperplasia (5x risk), sclerosing adenosis o Benign tumour: intraductal papilloma, Phyllodes tumour • Genetics (10%, AD) o BRCA1/2: 85% lifetime risk, risk of CA breast (triple negative), ovary (BRCA1), male breast, prostate, pancreas, melanoma (BRCA2); Mx: prophylactic bilateral mastectomy, BSO, PARP1 inhibitor o TP53 germline mutation: Li Fraumeni syndrome o PTEN mutation: Cowden syndrome/ multiple hamartoma syndrome o Peutz-Jeghers syndrome **BRCA1 gene mutation patient has higher possibility of triple negative CA breast**

Answer 5

• Incidence: M:F = 1:100 • Average age at diagnosis: 65 • Risk factors o BRCA2 carriers o Increased oestrogen: oestrogen therapy, etc o Radiation o Klinefelter's syndrome (XXY) • Management: mastectomy + SLNB/ ALND (if clinically +ve LN)

Answer 6

Investigations • Triple assessment, including bilateral mammogram (for synchronous contralateral breast cancer) • Bloods: LFT (liver met), CaPO4 (bone met) • Tumour markers: CA15.3, CEA • Staging: CXR, PET-CT, bone scan

Answer 7

• Clinical staging: tumour size, chest wall invasion, axillary LN metastasis • Pathological staging: core biopsy + sentinel LN assessment (see separate section) Tumour (T) T0: no evidence of primary tumour - T1: tumour ≤ 2cm • T1a: tumor ≤ 0.5cm • T1b: 0.5cm < tumor ≤ 1cm • T1c: 1cm < tumor ≤ 2cm - T2: 2cm < tumor ≤ 5cm - T3: tumour > 5cm - T4: tumour of any size, with direct extension to • T4a: chest wall (except pectoralis major alone) • T4b: skin (ulceration, edema i.e. Peau d’orange) but not meeting criteria of inflammatory CA breast • T4c: both chest wall & skin • T4d: inflammatory cancer (at least 1/3 of breast) Node (N) N0: no regional LN involvement N1: movable ipsilateral axillary nodes N2: fixed ipsilateral axillary nodes / internal mammary nodes only • N2a: Level I/II axillary LN • N2b: internal mammary LN without axillary LN N3: • N3a: Level III axillary LN only • N3b: internal mammary LN + axillary LN • N3c: supraclavicular LN Metastasis (M) M0: no distant metastasis M1: with distant metastasis Summary for staging • T1N0 —> Stage Ia • TxN1 —> at least Stage II • T4Nx —> Stage IIIb • TxN3 —> Stage IIIc Terms • Early: T1/T2, N0/N1 • Locally advanced: T4 or above Number of axillary LN metastasis is the strongest prognostic factor • N0: 5-year survival ~70% • The more lymph nodes, the worse 5-year survival

Answer 8

Surgery - BCS + post-op RT - Mastectomy (+/- skin flap) + Sentinel LN biopsy (clinically -ve LN) / Axillary LN dissection (clinically +ve LN)

Answer 9

• Patient factors: age, menopausal status, medical co-morbidities (esp. cardiac & renal), family / social • Tumour factors: size, axillary LN status, ER/PR/HER2 status, tumor histology & grading (Ki67), resection margin, operation done (BCS vs MRM), genomic studies Adjuvant therapy 1. RT 2. Chemo - Indications: positive LN, high risk CA (e.g. T2+), HER2+ if >1cm, Triple negative if >0.5cm - Regimen: Anthracyclines + Cyclophosphamide x 4 cycles —> Taxanes x 4 cycles • Each cycle is 3 weeks • Add cabecitabine if received neoadjuvant - S/E: • General: n/v, alopecia, mucositis (oral, diarrhoea), BM suppression, infertility, leukemia • A: cardiotoxicity (Mx: dexrazoxane) • C: haemorrhagic cystitis, premature ovarian failure • T: neuropathy, myalgia/ arthralgia 3. Hormonal therapy - Indications: All ER/PR+ cases unless C/I - Pre-menopausal at diagnosis : 10 years, otherwise 5 years • Seletive estrogen receptr modulator (SERM)(e.g. tamoxifen): S/E weight gain, flushing, risk of CA corpus, VTE • Aromatase inhibitor (e.g. letrozole, anastrozole, exemestane): post-menopausal only, S/E fracture, more effective than tamoxifen • GnRH analogue: pre-menopausal, Combine with tamoxifen / exemestane: more effective but more S/E • Radiation / Oophorectomy (rarely done) **NOT given concurrently with chemo: stop breast tissue proliferation —> affect uptake of chemo 4. Targeted therapy - HER2 +ve (strong) (20-25% of CA breast) —> Trastuzumab (Herceptin): IV infusion Q1mo x 12; S/E cardiotoxicity (not used concurrently with anthracycline), hypersensitivity reaction - High risk BRCA carriers —> PARP inhibitors e.g. olaparib - High risk ER +ve —> CDK4/6 inhibitors e.g. abemaciclib Neoadjumant therapy - Chemo +/- Herceptin (if HER2 +ve) - indications: locally advanced disease that is inoperable, large operable tumour that may be converted from mastectomy to BCS - Mark the location of tumor with metal clip / radioactive seed in case it becomes undetectable after Tx Advantages of neoadjuvant Tx: • Tumor shrinkage —> Reduce extent of surgery • Provide prognostic information • Allow addition of different adjuvant regimens Disadvantages of neoadjuvant Tx: • No proven benefit c.f. standard therapy • May upstage if no response to treatment Palliative therapy 1. Hormonal - ER/PR +ve - May be used with targeted therapy (HER2) 2. Bone Tx: - Bone met - Bisphosphonates, e.g. pamidronic acid RANKL inhibitor, e.g. denosumab 3. Chemo - organ met, e.g. liver, lung 4. RT - brain metastasis, cord compression, SVCO - steroids can also be given for brain met

Answer 10

Overview • Adenocarcinoma arising in the peripheral zone of the gland • 3rd MC cancer among males in HK, lifetime risk: 1/26, annual incidence: ~2300 • 1/3 is locally advanced / metastatic upon presentation Risk factors: • Advanced age • Smoking • FHx (age & number of FDR) • Genetics: TMPRSS2-ETS fusion gene (50%) Clinical features • Incidental findings: abnormal DRE, elevated PSA o DRE (only 25% palpable): asymmetrically enlarged irregular prostate, hard nodule, midline sulcus lost • Obstructive LUTS (late findings - cancer arises in peripheral zone) • Haematuria / haemospermia, new-onset erectile dysfunction • Metastasis: bone (vertebra: via Batson's venous plexus), liver, adrenal

Answer 11

• PSA (arbitrary cutoff at < 4 ng/mL) o Higher level = greater chance of CA prostate & higher risk of advanced disease Controversy of PSA • Organ-specific but not tumor-specific • Function of PSA: liquefy semen coagulum • Upper normal limit should be age-related • Factors affecting PSA level o ↑PSA: CA prostate, BPH, AROU, UTI, vigorous cycling, recent ejaculation <48h, DRE o ↓PSA: castration, 5α reductase inhibitors, prostate RT • PSA screening: o Not for age < 40 or >77 (with life-expectancy < 10 years) o May be considered for age 55-77 o May be considered for age 40-55 with family history • Prostate health index (PHI) if PSA 4-10 + normal DRE o Components: total PSA, free PSA, P2PSA (cancer-specific) o >35: proceed to prostate biopsy • Prostate biopsy: o Indications: - Elevated PSA > 10 - Abnormal DRE - PHI > 35 - Early CA prostate on active surveillance - Abnormal MRI prostate (PI-RADS 4-5) o Approach: transrectal (with TRUS or MRI), transperineal (TPUS or MRI) - “Fusion biopsy”: combine MRI image with USG o Check MSU 1 week prior to procedure: treat UTI if +ve o Take 12-18 random systematic biopsies o Complications: - Bleeding: haematuria, PR bleed, haemospermia - Infection (<0.5% for transperineal, ~5% for transrectal: antibiotic prophylaxis with FQ required) - AROU (1-2%): pain and swelling of prostate o Grading: Gleason score (1-5, sum of 2 most common histological patterns) - Further classified into 5 groups for prognostication: higher group = more likely to have non-organ-confined disease • Multiparametric MRI prostate o 3 sequences: T2-weighted, DWI with ADC (apparent diffusion coefficient), DCE (dynamic contrast-enhanced) o PI-RADS system: score from 1-5 o Roles: determine need of biopsy in controversial cases (PI-RADS 4, 5 indicated); local staging

Answer 12

AJCC 8th edition staging system • Combined use of TNM, serum PSA level & Gleason group • T staging o T1: clinically undetectable (normal DRE) o T2: palpable on DRE but confined to prostate o T3: spread beyond prostatic capsule (e.g. T3b = seminal vesicle invasion) o T4: invade to pelvic side wall Staging workup: depend on risk stratification Localised: 1. Low risk - PSA < 10ng/ml - GS < 7 - T1-2a 2. Intermediate risk - PSA 10-20ng/ml - GS = 7 - T2b 3. High risk - PSA > 20ng/ml - GS > 7 - T2c Locally advanced - any PSA - any GS - T3-4 or N+ • Low risk: Multiparametric MRI prostate • High risk (e.g. PSA > 20, GS ≥ 8): PET-CT with PSMA (prostate-specific membrane antigen), c.f. FDG o Superior to CT abdomen & pelvis + CXR + bone scan (Technetium-99 bone scintigraphy) – HA practice

Answer 13

Patient factor: age, co-morbidities Disease factors: PSA, DRE findings, Gleason score 1. Active surveillance - Regular FU with serial DRE, PSA & biopsy for Gleason score —> Offer RP/ RT only if worsen —> Avoid early Tx-related complications - preferred in low risk localised disease - limitations: disease progression; risk associated with repeated biopsy 2. Radical prostatectomy - Robotic-assisted resection of prostate gland + seminal vesicles + ampulla of vas deferens ± pelvic LN dissection in obturator & iliac regions (only for staging in high risk; no benefit in overall survival); Anastomosis of bladder neck & urethral stump - preferred in young < 75yr, high risk disease - early limitations: bleeding, UTI, rectal injury (1%), ureteric injury - late limitations: stress urinary incontinence (10%), erectile dysfunction (50%), anastomotic stricture (urethra, bladder neck), residual tumor / recurrence 3. Radiotherapy (EBRT / brachytherapy) - Avoid risk of GA and surgery but equivalent oncological control - preferred in older - limitations: ↓ Stress UI, similar ED c.f. RP ↑Irritative symptoms (FUN), radiation proctitis, radiation cystitis

Answer 14

Watchful waiting - for life expectancy < 10yr

Answer 15

Choice of treatment: • Traditional approach: ADT monotherapy first —> add others if CRPC • New approach: upfront chemohormonal therapy to destroy potential CRPC clones 1. Androgen deprivation therapy (ADT) • Surgical castration: bilateral simple orchidectomy (access via scrotal incision) • Medical castration: traditionally use estrogens - LHRH agonist (e.g. goserelin) + short-term antiandrogen cover (e.g. flutamide x 4/52) —> MoA: Downregulate gonadal axis (constant dose to mask normal LHRH pulsatility) —> Dosing: Q3-6m (more convenient) —> Pros: cheaper - LHRH antagonist (e.g. degarelix) —> Dosing: Q1m —> Pros: faster onset, less CV risk • S/E: osteoporosis, metabolic syndrome, thromboembolism, erectile dysfunction - cord compression patient may preferred antagonist, to prevent the original flare up 2. Chemotherapy - Add if patient young & fit with good RFT; improve survival if high-volume metastases • Docetaxel • Cabazitaxel 3. Androgen receptor targeted agents (ARTA) • Abiraterone: CYP17 inhibitor, need maintenance steroids to prevent adrenal crisis • Enzalutamide: potent multi-targeted AR antagonist • Apalutamide 4. Others: • Sipuleucel T: immunotherapy • Radium 223: with bone-seeking element • Lutetium-177 (177Lu)-PSMA

Answer 16

• Mechanisms: o Adrenal production of minor androgens o Tumor upregulation of androgen receptors o Tumor cells produce ectopic androgens

Answer 17

Overview • Most common renal neoplasm (only 20% renal masses are benign: e.g. oncocytoma, angiomyolipoma) • Prevalence of kidney cancers: RCC (MC) >> TCC renal pelvis > nephroblastoma (Wilm’s tumor) Pathology • Clear cell carcinoma (85%) – usually found in proximal tubule • Others: papillary (10%), chromophobe, collecting duct (poor prognosis) Risk factors • Smoking, HT, obesity • Occupation (petroleum) • Genetics: von-Hippel-Lindau (VHL - AD, bilateral RCC), tuberous sclerosis, PKD • Acquired cystic diseases (long-term HD/PD) • Renal transplant on immunosuppressants Clinical features: often asymptomatic until advanced disease • Incidental finding on imaging (50-60%) • Classical triad (10-20%): haematuria + flank pain + palpable renal mass • Regional involvement: uniquely invade into renal vein, IVC, RA o Left secondary varicocele: invasion to left renal vein o LL edema, ascites, pulmonary embolism • Metastasis: retroperitoneal LN, lung, bone, brain • Paraneoplastic syndrome (common, 6-10%) o Anemia (advanced disease), polycythemia, erythrocytosis o Hypercalcemia (PTHrP) o HT (ectopic renin) o Cushing’s syndrome (ectopic ACTH) moon face, hyperpigmentation, striae, thinning of skin, easy bruising, slow healing, infection, acne o Hypoglycemia o Gynaecomastia/amenorrhea/libido loss/baldness (ectopic gonadotrophin) F: hirsuitism, irregular menses M: ↓ libido/ fertility, erectile dysfunction o hypercalcemia o Pyrexia of unknown origin o Stauffer’s syndrome: non-metastatic hepatic dysfunction; impaired LFT (ALP) in the presence of a RCC (cholestasis) o Acquired dysfibrinogenemia

Answer 18

• Diagnostic: CT abdomen with contrast —> nephrectomy for pathology o Classical appearance: renal parenchymal mass with thickened irregular walls and contrast enhancement o Role of USG: determine cystic vs solid (e.g. fat-filled – likely AML) o Renal mass biopsy is usually NOT indicated: risk of bleeding, tumor seedling, false negative results (20%) • Suspected lymphoma • Metastatic RCC in poor surgical candidate (guide Tx) • Suspected renal abscess • Strongly enhancing extrarenal primary lesion (e.g. lung, liver, colon, melanoma) • Staging: CT T+A+P with contrast / PET-CT scan • Prognostic: Fuhrman's grading (nuclear size) Ix: - CT-guided biopsy - molecular diagnosis —> 1. PDL1 score 2. VHL positive 3. PIK3CAm positive

Answer 19

TNM staging • T1: ≤ 7cm (T1a: ≤4cm, T1b: 4-7cm), within kidney • T2: > 7cm (T2a: 7-10cm, T2b: >10cm), within kidney • T3: extend into perinephric tissues or major veins including IVC • T4: extend beyond Gerota’s fascia (fibrous tissue that encapsulates kidney and adrenal gland) and/or into ipsilateral adrenal gland Mx: - pembrolizumab (immunotherapy) + sunitinib (anti-VEGF) - nephrectomy only if minimal extrarenal disease • Targeted therapy o Sunitinib/ Softeinib - Only for clear cell carcinoma o Bevacizumab - Anti-VEGF monoclonal antibody - (also used in metastatic CRC) o Temsirolimus/ Everolimus - mTOR inhibitor • Immunotherapy o Interleukin-2 - S/E: fever, malaise, vomiting, diarrhoea o Interferon alpha o Lymphokine activated killer cells • Radiotherapy for bone metastasis Prognosis • Early-stage kidney cancer: 5-year survival rates in excess of 90% • ~10% of in distant metastases (poor prognosis)

Answer 20

Epidemiology • Common in male of 60-70, M:F = 3:1 • SCC most common in HK (90%) c.f. Western countries • Prognosis poor: > 50% metastasis at presentation, 5-year survival is just 5-10% Classifications: 1. Squamous cell carcinoma (Asia) - Site: mostly in upper 2/3 - Risk factors: Lifestyle: smoking, alcohol, hot drink, nitrosamine, betel nut, corrosive / caustic injury Oesophageal disorders: achalasia, Plummer- Vinson syndrome^, long-standing esophagitis Genetics: tylosis ( AD genetic disorder characterised by hyperkeratosis of palms & soles + oral leukoplakia) - Mx: sensitive to chemoRT 2. Adenocarcinoma (Caucasian) - Sites: mostly in lower 1/3 - Risk factors: GERD, Barrett esophagus - Mx: surgery, less sensitive to chemoRT Tumour spread: Direct extension (e.g. tracheo-esophageal fistula), Vascular and lymphatics Clinical features • Painless progressive dysphagia (MC): ≥75% stenosis • Odynophagia: usually due to extra-esophageal involvement • UGIB: haematemesis, coffee ground vomiting, tarry stool, anemic symptoms • Regurgitation / choking / aspiration pneumonia: due to esophageal obstruction • Signs suggestive of locally advanced disease: o Stridor / hoarseness of voice: vocal cord paralysis (usually left RLN palsy) o Horner’s syndrome o Respiratory symptoms: tracheo-esophageal fistula o Hypercalcaemia: HHM - PTHrP (10%) o Distant metastasis: Virchow's node, liver (hepatomegaly + ascites), lung (hemoptysis, PE), bone

Answer 21

• Diagnosis: OGD + biopsy: confirmatory histological diagnosis and pre-op assessment • Staging work-up: EUS + PET-CT (neck + thorax + abdomen) o Endoscopic ultrasound (EUS): best for T & N staging —> determine need of neoadjuvant chemoRT • T: Assess depth of wall invasion: important to distinguish T1a vs T1b (need open surgery) • N: EUS-guided FNAC of suspicious LN (hypoechoic, >1cm, spherical, homogenous) • Can also implant metallic markers for delineation of RT o CT whole body with contrast: for locoregional involvement (T3/4) and distant metastasis (M) o PET-CT: similar sensitivity as CT for distant metastasis (M) • Can also assess the metabolic activity after neoadjuvant chemoRT / detect recurrence • May pick up additional signals (e.g. reactive hilar LN due to smoking) o ± USG neck o ± Diagnostic laparoscopy: recommended for OGJ tumors (adenoCA) for hepatic / peritoneal seeding o ± Bronchoscopy: for cervical / upper thoracic tumors to detect tracheal invasion à may require stenting before RT to prevent iatrogenic tracheo-esophageal fistula • Others: o CBC, LRFT, clotting o Lung function (CXR, ABG, lung function test) for pre-op assessment o Laryngoscopy: baseline vocal cord status

Answer 22

• Tumor factor (staging) • Patient factor: age, smoker, comorbidities, lung function (FEV1 > 1.5L), exercise tolerance (> 2 flight of stairs) • Organ factor: method of reconstructing esophagus Stage 0: - Tis, N0, M0 Stage 1: - T1, N0, M0 —> Tis/T1a (confined to mucosa): Endoscopic mucosal resection (EMR) / Endoscopic Submucosal dissection (ESD) —> T1b (invades submucosa): esophagectomy Stage 2: - T2-3, N0, M0 - T1-2, N1, M0 Stage 3: - T3, any N, M0 —> Operable SCC: neoadjuvant chemoRT + esophagectomy —> Inoperable SCC: upfront chemoRT +/- esophagectomy (if downstaged) —> Operable ADC: esophagectomy —> Inoperable ADC: chemoRT Stage 4: - any T, any N, M1 —> Esophageal balloon dilation +/- stenting —> Palliative chemoRT 1. Esophagectomy - Two-staged - Three-staged - preferred for SCC 2. Neoadjuvant therapy • Indication: locally advanced SCC – T2N1, T3N0, T3N1 • Regimen: 5-fluorouracil + cisplatin + 40 Gy RT o 6-8 weeks for 2 courses —> wait 4 weeks and repeat PET-CT + OGD —> wait 4 weeks for surgery • S/E: RT-induced fibrosis, worsened dysphagia 3. Primary ChemoRT • Indication: inoperable SCC, not fit (e.g. poor lung function) • Regimen: cisplatin + 5-fluorouracil + >50 Gy RT Palliative treatments • Endoscopic stenting: • Endoscopic local ablation • Nutritional support: NG tube / PEG tube / open gastrostomy / jejunostomy • External radiotherapy / brachytherapy (intraluminal RT)

Answer 23

Epidemiology • Incidence: ↓ trend (6th incidence, 4th mortality), but ↑ in Asia (Japan: diet-related) • Cell type: adenocarcinoma (90%) > lymphoma (5%) > GIST, metastasis • Site: distal stomach (antrum / pylorus) > cardia (↑ trend) > OGJ Risk factors: • Compensatory epithelial cell proliferation: - H. pylori - Chronic gastric reflux (e.g. Barrett’s esophagus): proximal CA - Hx of gastric resection: bile reflux (e.g. Billroth II) - Chronic atrophic gastritis: a/w pernicious anemia and Menetrier’s disease • Environmental factors: smoking, smoked / pickled food, nitrosamines, alcohol • Host factors: hereditary diffuse gastric carcinoma (HDGC: E-cadherin mutation), HNPCC, FAP, P-J syndrome Classifications: Histological (Lauren classification) - Intestinal type (well-differentiated, better Px) Risk factors as above except FHx and HDGC HER2+ve in 15% Hematogenonus spread Elderly male, distal stomach - Diffuse type (undifferentiated, poorer Px) Risk factors: HDGC HER2-ve Transmural and lymphatic spread Young female, proximal stomach Clinical features: • Local: dyspepsia, early satiety, bloating, n/v, constitutional symptoms • Complications: obstruction (dysphagia if proximal, GOO if distal), UGIB, perforation • 4 routes of metastasis: o Local spread: pancreas, transverse colon, liver, duodenum o Lymphatic spread: peri-gastric / para-aortic nodes, Virchow's node, Sister Mary Joseph nodule (periumbilical node), Irish node (left axillary node) o Haematogenous spread via portal venous circulation: liver (hepatosplenomegaly, jaundice) —> lung, bone and brain o Transcoelomic spread: ascites, ovaries (Krukenberg’s tumors), pouch of Douglas (Blumer’s shelf) • Paraneoplastic for GI adenoCA (e.g. gastric, pancreatic): o Trousseau’s sign of malignancy (migratory thrombophlebitis) o Leser-Trelat sign: seborrheic keratosis o Acanthosis nigricans

Answer 24

• Diagnostic: OGD + biopsy o Obtain tissue diagnosis and evaluate extent of primary tumor o Alternative: barium swallow (limited diagnostic value except for linitis plastica) • Staging (TNM): most important prognostic factor is depth of tumor invasion o CT abdomen + pelvis +/- thorax with contrast (thorax if proximal tumor e.g. cardia) • Mandatory for M staging but not accurate for T & N • Alternative: PET-CT – not too sensitive for CA stomach o Endoscopic ultrasound (EUS): NOT mandatory for CA stomach (upfront surgery is advocated) • More sensitive in T staging (e.g. differentiating T4a vs T4b) & N staging (e.g. perigastric LN) • More operator-dependent and more invasive c.f. CT o Staging laparoscopy + peritoneal lavage (routine) • More accurate for peritoneal and liver metastasis c.f. CT • Direct visualization +/- biopsy of suspicious lesions for frozen section • Peritoneal washing for cytology to detect microscopic peritoneal metastasis o CXR • Tumor markers: CEA, CA125, CA19-9 – for monitoring recurrence and response to chemotherapy • Pre-op bloods: CBC, LRFT, clotting

Answer 25

1. Endoscopic treatment - Endoscopic mucosal resection - Endoscopic submucosal dissection 2. Gastrectomy with 15 lymph nodes resection Non-surgical: • Neoadjuvant chemotherapy: downstage the tumor to improve resectability rate o HK: Upfront surgery is preferred – only consider if T3+ (not yet invade adjacent structures) / N+ (at least 1-2 lymph nodes) o Regimen: FLOT (fluorouracil + leucovorin (folinic acid) + oxaliplatin + docetaxel) / Xelox if less fit • Adjuvant chemotherapy: eradicate micro-metastasis o Consider if T3+ / N+ o Regimen: 5-fluorouracil (or: capecitabine) +/- oxaliplatin (i.e. Xelox) or TS-1 Palliative care • Tumors considered unresectable if: o Distal metastasis (e.g. multiple liver metastasis, peritoneal nodules, pelvic deposits, Virchow’s nodes) o Extensive nodal involvement (D3) o Invasion of major vessel, e.g. aorta, hepatic artery, coeliac axis, proximal splenic artery (not distal) • Distal splenic a.: borderline resectable with LUQ exenteration • Principles: relieve pain, nutrition, bleeding, obstruction, perforation • Supportive treatments: transfusion, PPI, Fe supplement • Endoscopic treatments o Ethanol injection, adrenaline, clipping: for bleeding o Metallic stenting: bypass obstructing tumor, but risk of re-stenosis by tumour ingrowth • Palliative surgery o Palliative resection: relieve bleeding / obstruction o Palliative bypass (gastrojejunostomy / gastroenterostomy): more durable than stenting, but possible impaired gastric emptying / bile reflux • Palliative chemo +/- HER-2 inhibitor (if HER2 +ve) +/- ramucirumab (VEGFR2 antagonist) • External beam radiotherapy (EBRT) for painful bone metastases

Answer 26

• OGD: mass with smooth margins and normal overlying mucosa (endoscopic Bx typically cannot establish Dx) • Endoscopic ultrasound + fine needle aspiration (FNA) o EUS: hypoechoic, homogenous lesions arising from 2nd-4th layer of GI wall o Combined cytologic (histology: spindle cells) and IHC (CD117 + c-KIT mutation) o Not mandatory – indicated if: • Consider use of imatinib for unresectable / metastatic disease • Consider neoadjuvant imatinib for large GIST • GIST 1-2cm: obtain mitotic index risk stratification • Percutaneous biopsy is NOT preferred: risk of tumour capsule rupture with peritoneal spread • Staging: CT with contrast (MRI if at rectum or liver)

Answer 27

• Surgical resection: negative margins are adequate o Indications: all GIST ≥ 2cm o Approach: segmental resection (regional lymphadenectomy not required - rarely metastasized to LN) • Explore abdomen during laparotomy to exclude liver / peritoneal metastases • Avoid perforating capsule: chemo may be needed • Tyrosine kinase inhibitor (first line: imatinib à acquired resistance: sunitinib) o Adjuvant: in all high-risk cases e.g. perforated capsule o Neoadjuvant: 3-6 month therapy for locally advanced/ metastatic (liver or peritoneal mets) potentially resectable tumours (↓size & vascularity of tumors —> ↑organ preservation) o Palliative: first-line treatment for metastatic GIST Malignant potential of GIST depends on AFIP prognostic model: • Location (SB most likely malignant) • Size • Mitotic index • Tumor rupture

Answer 28

Metastasis: liver, peritoneum Clinical features: incidental finding on OGD/CT - GI bleed - Abdominal pain - Abdominal mass

Answer 29

Risk factors • Non-modifiable: age > 50, gender (male) • Central obesity, sedentary lifestyle, diet (increased fat & red meat, reduced fibre), smoking • GI: IBD (UC > CD), polyps • Endocrine: DM, acromegaly (IGF-1 as growth factors for colonic mucosal cells) • Family history: 25% have FHx; 10% have familial syndrome (FAP, Lynch syndrome) • Protected factors: prolonged aspirin/ NSAID use Clinical features • Most commonly asymptomatic à detected by screening • Different presentations between right-sided and left-sided lesions Right-sided (Proximal): present later - Tend to bleed (larger calibre, polypoid lesion) - Iron deficiency anemia, dull vague abdominal pain, right-sided abdominal mass - Not common to have change in bowel habits (stool is more liquid and colon more space on right side) Left-sided (Distal): present earlier - Tend to obstruct (smaller calibre, annular lesion) - Change in bowel habits (tenesmus, reduced stool calibre, mucoid stool) - Hematochezia, intestinal obstruction • Metastasis: o Direct spread: radial (implicated in resectability in rectal cancer) o Lymphatic spread: Virchow's node (Troisier's sign) o Haematogenous spread: liver (MC), lung (distal rectal tumour —> IVC —> lung) o Transcoelomic spread: ovary (Krukenberg tumour), pouch of Douglas

Answer 30

• Bloods: CBC D/C (anemia), Fe profile, LFT (liver met), RFT • Serum carcinoembryonic antigen (CEA): epithelial marker o Cut-off: <4.7 o Low diagnostic ability: low sensitivity + low specificity for CRC - Elevated in ~50% of CRC only: may be first-pass metabolized by liver - False positive: pregnancy, smoking, TB, IBD, other carcinomas (e.g. GI tract, pancreas, breast) o Post-op: take 4-6 weeks to return to normal o Roles: prognostication, treatment monitoring and detection of recurrence (even if pre-op normal: can pick up non-portovenous distant metastases e.g. lung) • Diagnostic: colonoscopy with biopsy (gold standard) o Confirm diagnosis with histological evidence o Exclude synchronous cancers (3-5%) and synchronous polyps (30-50%) o Pre-op localization (esp. if tumor is very small): tattooing (inject ink to stain tumor) • CT colonoscopy: when caecum cannot be reached by CLN o Pros: similar diagnostic accuracy for tumors >1cm, extraluminal info, lower risk of perforation o Cons: high radiation dose, not therapeutic (still need CLN to take biopsy) • Double-contrast barium enema (DCBE): barium + air o Superseded by CT colonography: risk of barium peritonitis o Classical findings: "apple core" lesion – near-circumferential involvement of bowel walls • Biomarker: for metastatic disease only o KRAS & NRAS (signalling downstream of EGFR): mutated in 45% —> no response to anti-EGFR o MMR: MMR-deficient/ MSI (microsatellite instability) —> PD-1 pathway inhibitors

Answer 31

Staging: • Objectives o Determine resectability o Select patients for neoadjuvant therapy / local excision o Most important prognostic factor • Colon cancer: o CT thorax + abdomen + pelvis with contrast: Most sensitive for T-staging, can also give N and M staging o Alternative: PET-CT with contrast: better for detecting distant metastasis, also used for follow-up (localizing site of recurrence if ↑CEA) o Other adjuncts: Bone scan, CXR and liver USG, liver MRI with contrast • Rectal cancer: o MRI pelvis: important for accurate T-staging for planning of neoadjuvant chemoRT —> Assess extra-mucosal tumor invasion (EMTI): MRI is superior to CT in delineating mesorectal fat —> Determine circumferential resection margin (CRM) o Alternative: Endorectal ultrasound (EUS): only good for T staging, but operator-dependent and might not admit endoscope for obstructive tumors • TNM staging: o I: T1/2 N0 o II: T3/4 N0 o III: N1/N2 o IV: M1 Management overview • Stage I: surgery + analysis of ≥12 LN • Stage II: surgery +/- adjuvant chemo (consider in high-risk stage II) • Stage III: surgery + adjuvant chemo (FOLFOX) +/- adjuvant RT (rectal only) +/- neoadjuvant chemoRT (in high risk rectal only*) • Stage IV: chemo +/- surgery for isolated liver metastasis

Answer 32

1. Surgery - right lesions: right-hemicolectomy - left lesion: extended right, left hemi, sigmoidectomy, emergency: Hartmann’s operation 2. Adjuvant chemotherapy o Options • FOLFOX for 6 months: folinic acid + 5-fluorouracil + oxaliplatin • Xelox for 3 months if lower risk (T1-3, N1): o Indications: Stage 3 (N1+), high risk stage 2 (T4 tumor, lymphovascular invasion, poor histology)

Answer 33

1. Surgery - local excision for T1N0 disease - sphincter-preserving surgeries: —> Indicated if: T2-4 + adequate pre-op sphincter function + adequate distal margins —> Anterior resection / lower anterior resection + total mesorectal excision - abdominal perineal resection: Indicated if ANY one of: poor pre-op sphincter function / failure to achieve negative distal margin / locally advanced or recurrent low-lying CA rectum 2. Neoadjuvant therapy o 3 main indications • Resectable but locally advanced disease: sterilize tumour bed, ↓ intra-op tumor spillage & ↓ local recurrence rate • T3/T4 disease • Nodal disease • Threatened CRM (circumferential resection margin) (<2mm) • Borderline resectable disease: downstage the tumor and ↑ resectability rate • Low-lying tumor: downsize the tumor and ↑ sphincter preservation rate Regimen: 5-FU based chemotherapy x 2 cycles + concurrent RT (50.4 Gy = 1.8 Gy daily x 28 fractions) —> Wait 8-10 weeks before surgery —> 4 cycles of chemo as adjuvant Disadvantages: Max dose of RT for lifetime Delay surgery Remission after neoadjuvant chemoRT • Clinical complete remission (CCR) ~20%: consider “watch and wait” for 3 years with MRI Q3m, flexible sigmoidoscopy Q3m, PET-CT / CT Q6m • Pathological complete remission (PCR) ~15%: surgical specimen found to be tumor-free, may not require adjuvant chemo (case-by-case) • Adjuvant chemotherapy: First-line is 5-FU based, other options include oxaliplatin, irinotecan, cetuximab • Adjuvant radiotherapy: not common

Answer 34

Palliative management for colorectal cancer • Palliative surgery o Endoluminal stenting: for palliating obstruction / bridging therapy before elective surgery (avoid EOT) • Not for distal rectal tumour (can cause tenesmus and pain) o Palliative colostomy +/- tumor resection (palliative intent) • Palliative radiotherapy: control local symptoms (e.g. pain, discharge, bleeding, incontinence) and bone pain • Palliative chemotherapy for disseminated disease: oral capecitabine Management principles of metastases • Liver / Lung metastases: resect if possible (solitary metastasis, no other mets, controlled primary tumor) o Refer to HBP for management of colorectal liver mets

Answer 35

Follow-up for colorectal cancer • Aim: detect recurrence (40%) and metachronous tumors (new primary CA diagnosed 6mo afterwards) • Follow-up interval: o First 2 years: Q3m o 3rd year: Q6m o 4-5th year: yearly o >5 years: considered to be in remission • Investigations in each follow-up: o CEA, rigid sigmoidoscopy, LFT o CT TAP/ PET-CT Q1y o Colonoscopy: • Pre-op not full scope: within 6m of surgery (risk of synchronous tumour in CA rectum = 3-5%) • Pre-op full scope: 1 year post-op, then at 3 years, 5 years, then Q5y

Answer 36

Overview • MC primary liver cancer (80%) (intrahepatic cholangiocarcinoma 15%), 5th MC cancer in HK, 3rd in mortality cancer • Patterns: solitary / multifocal / diffuse • Histological subtype: o Non-fibrolamellar: a/w HBV and cirrhosis liver cirrhosis o Fibrolamellar (FLC): a/w younger patients, not a/w HBV or cirrhosis; Risk factors • Any cause of cirrhosis: infection (HBV, HCV), metabolic (ALD, NAFLD, Wilson’s disease), immune (PBC, PSC) o HBV infection carcinogenic in terms of cirrhosis + DNA damage induced by HBV DNA integration • Smoking, alcohol (free radical production) • Obesity, DM (liver involved in glucose metabolism) • Chemical carcinogens, e.g. aflatoxin Clinical features: late presentation + absence of pathognomonic symptoms —> difficult diagnosis • Local: o RUQ pain +/- right shoulder pain (2o to Glisson’s capsule distension) o Hepatomegaly o Obstructive jaundice (invasion to biliary tree or compression of intrahepatic duct) – NOT common o Constitutional symptoms: LOA, LOW hepatorenal syndrome • Paraneoplastic syndromes: o Erythrocytosis (EPO secretion from tumour) o Hypoglycaemia (high metabolic demands of tumour + IGF-2 secretion) o Deranged LFT in cirrhotic patients: e.g. encephalopathy, coagulopathy, portal HT (ascites, edema, UGIB), o Hypercholesterolemia (autonomous cholesterol synthesis) o Hypercalcaemia (PTHrP secretion) o Watery diarrhoea (VIP secretion) o Cutaneous features: dermatomyositis, Leser-Trelat sign (explosive onset of multiple seborrheic keratoses) • Ruptured HCC • Metastasis: intrahepatic (via portal vein / hepatic vein), lung (MC), bone, brain, peritoneum, adrenals

Answer 37

• Bloods: CBC, clotting, LRFT, albumin • Viral serology for underlying chronic hepatitis o HBV: HBV DNA, HBsAg, HBeAg (↑risk of HCC) o HCV: anti-HCV IgG, HCV RNA • AFP: normal <6 (raised in 80%), level correlates with prognosis (risk of recurrence) o False positive AFP: pregnancy, germ cell tumor / teratoma, liver cirrhosis, hepatitis, • USG HBP: screening for HCC (any nodule that is not clearly hemangioma = HCC until proven otherwise) o Mass < 1cm: repeat USG Q6m (rationale: tumor doubling time ~4 months) o Mass ≥ 1cm: triphasic CT • Triphasic CT scan (gold standard) - Arterial phase: hyper dense - Portovenous phase: washout - Delayed phase: hypodense • MRI liver with Primovist contrast (hepatospecific contrast) - if CT C/I or equivocal findings o Typical features: high intensity on T2-weighted and low intensity on T1-weighted images • Contrast-enhanced USG • CT hepatic angiography: inject intraarterial contrast (e.g. SMA, hepatic a.) • Post-lipiodol CT scan: HCC shows up on Day 10 due to lack of Kupffer cells to ingest lipiodol • Percutaneous liver biopsy: Only done in inconclusive diagnosis and unresectable cases (e.g. differentiate primary from secondary tumors) o Contraindications: bleeding tendency (e.g. INR > 1.2 despite vit K), thrombocytopenia (Plt < 50), high- grade biliary obstruction (risk of bile peritonitis) o Risk of bleeding (hypervascular tumour), organ puncture, needle tract seeding of tumour For staging: • Imaging: triphasic CT, bone scan o PET-CT: limited sensitivity as HCC does not take up FDG well and liver has high background metabolic activity —> require dual-tracer ([11C]-acetate + [18F]-FDG) - taken up by tumour cells at varying degrees • TNM staging For complications: • CBC: low Hb, Plt (hypersplenism) • Child-Pugh score (albumin, bilirubin, clotting, distended abdomen, encephalopathy)

Answer 38

1. Liver resection 2. Liver transplant 3. Local ablation • Roles: Potentially curative, bridge therapy to transplant, or palliative • Radiofrequency ablation (RFA) o Indications: small single tumour < 2cm (as alternative to resection – resection is preferred if 2-5cm), inoperable solitary HCC < 5cm, inoperable ≤3 nodules ≤3cm where transplant not feasible o Route: percutaneous, open o Contraindications: too close to major vessels / major bile ducts / diaphragm (if percutaneous) o Complications: bile duct injury, thermal injury to surrounding tissues • Other less commonly used: ethanol, microwave, high-intensity focused ultrasound (HIFU), cryotherapy 4. Trans-arterial chemoembolization • Based on the premise that tumour is mainly supplied by hepatic artery • Procedure: o Selective intra-arterial administration of chemotherapy e.g. cisplatin, doxorubicin (drug-eluting beads) • Emulsified with lipiodol: retain longer in HCC (no Kupffer cells to ingest) o Partial embolization of major tumor artery with Gelfoam: ↓ clearance of chemo, promote tumor necrosis • Indication: large (>5cm) + unresectable + Child A/B • Contraindications: portal vein thrombosis (—> liver ischaemia), Child’s C, distant metastasis, AV shunt to hepatic vein (—> risk of PE) • Complications: o Post-embolisation syndrome (within 14 days): liver injury due to tumour lysis or ischaemic damage to normal liver tissue; S/S fever, RUQ pain, anorexia; resolve spontaneously after 1 week o Liver failure: due to infarction of normal liver tissues o Bile duct injury o GI bleeding: cytotoxic reflux into other arterial supply to stomach • Alterative: transarterial radioembolization (TARE) with 90Yttrium 5. Others • Selective internal radiation therapy (SIRT): high-dose RT (3-6 fractions) to small inoperable HCC • Sorafenib: multitargeted kinase inhibitor (e.g. Raf, VEGF, PDGF) o Prolonged survival by 3 months [SHARP trial] o Side effects: hand-foot syndrome (acral erythema) o Alternatives: other TKI (e.g. regorafenib / lenvatinib), single-agents (e.g. doxorubicin, cisplatin), bevacizum 6. Immunotherapy

Answer 39

Types • Ductal adenocarcinoma (90%) • Cystic tumours, ampullary cell tumours, islet cell tumours: much better prognosis • Metastasis: from RCC (MC), lung, breast Sites: head (60%), body (15%), tail (5%), diffuse (20%) Risk factors • Smoking (3x risk) • DM, chronic pancreatitis • FHx • Pre-malignant conditions e.g. pancreatic intraepithelial neoplasia (PanIN) • Hereditary cancer syndromes e.g. Lynch Clinical features • Painless progressive obstructive jaundice (tumor at head) • Severe epigastric pain radiating to the back (tumor at body/tail: retroperitoneal infiltration) • Constitutional symptoms • Symptoms of pancreatic insufficiency: e.g. steatorrhoea, maldigestion, malabsorption, new onset DM • Acute pancreatitis / GOO • Signs of metastasis: liver, peritoneum, lung, bone • Paraneoplastic manifestations o Trousseau syndrome: hypercoagulable state —> migratory superficial thrombophlebitis o Paraneoplastic pemphigoid Investigations • Bloods: CBC, clotting, LFT (cholestatic pattern), RFT, glucose, amylase, lipase • Tumor markers: o CA19.9 (raised in 80%): prognostic marker + monitoring after Tx • Low diagnostic value: not sensitive, not specific • Other causes: HCC, cholangioCA, CA gallbladder, chronic pancreatitis, cholangitis o CEA (raised in 30-60%) • Imaging: o USG (dilated bile ducts) o CT abdomen with contrast (pancreatic protocol) – thin-sliced tri-phasic (arterial + pancreatic + portovenous phases) • Double duct sign: dilated pancreatic duct + CBD • Hypoattentuating mass within pancreas • Determine resectability: encasement of SMA, hepatic artery, celiac trunk, SMV, PV o +/- MRCP: delineate anatomy of biliary tree • Tissue diagnosis: NOT mandatory if potentially resectable - only required if CT failed to demonstrate typical features, before chemotherapy, or suspected 2° mets to pancreas o EUS-guided FNAC/biopsy preferred over percutaneous USG/CT-guided biopsy (↑risk of tumor seeding) o ERCP brush cytology / biopsy: can also relieve jaundice by placing temporary stent • Staging: o CT T+A+P or PET/CT o Intra-op laparoscopy (peritoneal metastasis often missed in imaging) TNM staging • Resectable: stage 0 - IIB • Unresectable: stage III (T4) & IV o Stage III: longer survival, more beneficial from systemic therapy o Stage IV: shorter survival, less beneficial from systemic therapy Curative treatment Principle: Upfront pancreatectomy (+ local lymphadenectomy) + adjuvant chemotherapy (all cases) +/- RT 1. Pancreaticoduodenectomy (Whipple’s operation) 2. Adjuvant chemotherapy • Indications: ALL resected CA pancreas • Start within 12 weeks post-op o FOLFIRINOX (folinic acid, 5-FU, irinotecan, oxaliplatin) o Gemcitabine + capecitabine x 6 months

Answer 40

Epidemiology • Southeast Asia: 25 per 100000 • Western countries: 2 per 100000 Risk factors • Epstein-Barr Virus • Family history • Diet: preserved food, Salted fish • Smoking • ?HPV Screening • EBV DNA • EBV VCA (viral capsid antigen) Signs and symptoms - nasal obstruction - cranial nerve involvement (3,5,6,7 why not 6?) - neck mass - epistaxis - serous otitis media Hx: (new case) - Ear o Ear discharge o Hearing impairment (conductive hearing loss): tumor compressing on Eustachian tube o Tinnitus o Ear ache - Nose o Nasal obstruction o Postnasal drip o Epistaxis or blood-stained discharge - Throat o Neck mass o Dysphasia o Dyspnoea o Speech problem: hoarseness of voice o Swallowing, choking - Others o Headache o Facial numbness (CN 5) o Visual impairment: diplopia (CN 3, 4, 6) PE - Cranial nerves - Neck (LN) - Side effects of RT: scars, oral mucositis, etc. Classification 1. Keratinizing SCC CN12 fasciculation Dental gap trismus 23 2. Non-keratinizing - differentiated - undifferentiated (most common in HK 95%) 3. Basaloid SCCC (extremely rare)

Answer 41

Investigations Bloods: - CBC - LFT (esp ALP) - RFT: pre-chemo assessment (CrCl) - Uric acid (if rapidly growing?) - Serology (EBV DNA, EBV VCA); EBER (Epstein-Barr Virus Small RNA genes) - (EBV IgA, IgG against VCA, early antigen, nuclear antigen) Histology: - Nasopharyngoscopy ± Bx Imaging: - USG + FNAC - CT head & neck/MRI head & skullbase if intracranial extension suspected (fossa of rosenmuller, pharyngobasilar fascia obliteration, tumor invasion to soft tissues, skull base, sinuses, LN mets) o Or CT/MRI nasopharynx and neck (can also visualize cervical LN) o May need thin slice, contrast imaging - CT chest & upper abdomen (esp in px with high risk of distant metastasis I.e. Advanced nodal met N3) - PET scan, bone scan - Baseline audiogram

Answer 42

TNM staging - bilateral cervical LN (N2) Stage III - intracranial extension ± CNs involvement (T4) Stage IV - Large cervical LN >6cm or supraclavicular fossa LN Stage IV - N1 —> at least stage II

Answer 43

- Radiotherapy (mainstay) (+ bilateral neck irradiation) o Neuro - Carotid artery: stenosis, pseudoaneurysm, aneurysm (@ skull base: massive epistaxis), rupture - Temporal lobe radionecrosis • Memory loss, complex partial seizures - Autonomic dysfunction (sympathetic trunk at carotid body): fluctuating BP - CN palsy (CN 8, 9, 10, 11, 12) • Delayed bulbar palsy: dysarthria, dysphagia, tongue and palatal weakness, motor weakness of CN11 - Lhermitte’s syndrome • ∵ reversible demyelination of ascending sensory neurons due to inhibition of oligodendrocyte proliferation following RT of cervical or thoracic spine o Endocrine - panhypopituitarism (secondary) • Growth hormone —> Puberty cessation, fine wrinkles, obesity, muscle weakness • ACTH cortisol (2° adrenal insufficiency) o Anorexia, malaise, nausea, abdominal pain, postural hypotension, dizziness, hypoglycemia (hungry sensation, sweating) o Addisonian crisis: convulsion, psychosis, hypoNa, hyperK, hyperCa, severe vomiting & diarrhea, low BP, syncope, slurred speech, severe lethargy, hypoglycemia • ADH (Diabetes insipidus) o Polyuria, polydipsia, confusion • Prolactin o Galactorrhoea • Thyroid o Cold intolerance, weight gain, ↓ appetite, constipation, menorrhagia, depression, tiredness, lethargy, muscle aching & cramps, thinning of hair • Sex hormone o Loss of libido, infertility, oligomenorrhea, loss of body hair, osteoporosis, erectile dysfunction Primary hypothyroidism: fatigue, pretibial myxedema o MSK *Skull base osteoradionecrosis (osteomyelitis), *trismus o Ear - Otitis media effusion (Eustachian tube dysfunction) - small vessel disease (complete conductive hearing loss) - tinnitus o Nasopharynx Epistaxis: thinning of blood vessel wall o Others - Facial muscle fibrosis - Xerostomia: dry mouth (salivary gland) - skin changes (peeling), neck fibrosis/scarring - mucositis: oral, GIT - esophageal stricture - poor nutrition, dehydration (gastrostomy tube insertion - Secondary tumours, bone fibrosis - Chemotherapy: for advanced cases o Agents: cisplatin, 5-fluorouracil o Pre-chemo: HT, DM, IHD, HBV, HCV, HIV, TB o Chemo efficacy: initial symptoms o Chemo S/E: renal impairment, neuropathy, emesis, neutropenia, hematological toxicity, trismus (dental) - Concurrent chemoRT: for locoregionally advanced head and neck cancer to sensitive tumor to the effects of RT and thereby improve tumor control - Molecular targeted agents (under research): Cetuximab, Bevacizumab Early (Stage I): RT alone Intermediate (Stage II): concurrent chemoRT Advanced (Stage III, IVA & IVB): concurrent chemoRT ± adjuvant chemotherapy

Answer 44

Presentation: - Routine pap smear - Abnormal PVB (intermenstrual bleeding, post-coital bleeding, post-menopausal bleed) - Constitutional S/S, pressure or mass symptoms (stage 4) Dx - Bx of cervical lesions if any - Colposcopy if pap smear +Ve but no mass - cone Bx or endocervical curettage Ix - USG: hydronephrosis +/- cystoscopy +/- sigmoidoscopy Staging - MRI pelvis (T staging) + MRI /CT (N staging) + PETCT (extrapelvic disease) Mx: - Hysterectomy +/- BSO - Radiotherapy Primary RT: all except stage 1A; not preferred in 1B/ 2A (morbidity >> surgery) Concurrent chemoRT: tumor volume directed RT with additive weekly low dose cisplatin: —> More effective, higher morbidity —> For stage IB3; stage 2B or above Technique: IMRT (reduce morbidity, same cure) S/E: Radiation proctitis, cystitis, ↑secondary cancer Ovarian function, vaginal function (dyspareunia) Chemo: - Chemotherapy alone is for palliative Tx - Regimen: Carbotaxol (Carboplatin + Taxol) Target - Metastatic disease: bevacizumab + chemotherapy immunoTx - antiPD1, antiPDL1 (nivolumab) Risk factor - HPV16-18; multiple sexual partners; smoking, OCP , old age, immunocompromised Histology - SQCC 80%, ADC 20% Prognosis - I II III IV —> 90, 70, 40, 8 FU Q4-6m PE: abdo exam (mass/ ascites) + LNs + speculum + PV + PR Pap smear Q6m x 10yr

Answer 45

Risk factor: - Estrogen exposure, obesity, HT, DM, estrogen, TMX, PCOS Histology: - ADC 80% grade 1-3 (well to poorly differentiated) Symptoms: - PVB, PMB / IMB / menorrhagia PE: general + abdomen + speculum + bimanual + PR +/- respi (pleural effusion) Ix - Dx: endometrial sampling / uterine curettage - MRI A+P with contrast (better than CT, for soft tissue – myometrial & cervical invasion) - PETCT in high grade tumor Tx: Stage 1A grade 1: mirena, PO progesterone Stage I: TH +/- SO+ pelvic LN +/- para-aortic LN (Depending on grade) II: THBSO + pelvic radiation + brachytherapy OR radical hysterectomy + BSO + pelvic + para-aortic LN III: THBSO + LN removal (no need full dissection) + adjuvant chemoRT IV: palliative: - hysterectomy BSO / local RT for bleeding S/S - chemo (paclitaxel) +/- hormonal Tx Adjuvant Tx - Chemotherapy in stage III – IV or early stage high grade – carbotaxel FU Q4-6months - Symptoms, PE (LN, PV, PR, abdo, speculum x vaginal vault) PET CT if suspect - Prognosis 5YS: 70% (80, 65, 30, 10)

Answer 46

Risk factor: BRCA1/2, lynch syndrome nulliparous, age of first child >35, early menarche late menopause, obese, HRT ~CA breast Protective: - COCP , pregnancy. Breastfeeding, salpingectomy, sterilization Histology - Serous .>> mucinous > endometroid > Clear cell > Transitional cell Symptoms - 75% present in advanced stage – pelvic mass, abdo mass, pelvic pain, bloating PE: general exam + LN + respi (PE), abdomen (Ascites, mass), speculum, bimanual PR (POD Nodularity, fixed pelvis / frozen pelvis) Ix USG (TAS / TVS) Staging: CT A+P with contrast Tumor marker: CA125, CA19.9 (mucinous) Estimate RMI – risk of malignancy (USG + menopausal status + CA125) Staging FIGO staging I: tumor confined to ovary / fallopian tube II: pelvic extension / peritoneal cancer III: retroperitoneal LN / peritoneum macroscopic metastasis IV: distant met (excluding peritoneal met) pleural effusion, extra-abdominal LNs Tx - Stage I&II Staging laparotomy + debulking surgery (THBSO + omentectomy + peritoneal cytology + RP LN assessment) + adjuvant chemo (carbotaxel carboplatin + paclitaxel) 6 cycles Q3 weeks S/E: carboplatin: plt, nephrotoxicity, peripheral neuropathy Paclitaxel: neutropenia, nephrotoxicity, peripheral neuropathy, alopecia - Stage III-IV Debulking surgery or neoadjuvant surgery + interval debulking surgery Recurrence - Chemo response depends on time to recurrence —> Long time: re-try platinum agents —> Short time: 2nd line chemo (Doxorubicin) prognosis - 90% > 70% > 60% > 17% FU - Symptoms + PE + CA125 suspicion: USG, CT T+A+P or PET CT

Answer 47

Presentation: Painless LN enlargement (cervical > axillary); contiguous LN spread 50% present splenomegaly (usually NOT MASSIVE; due to REACTIVE; not infiltrate) Infiltrative S/S: ● Pancytopenia symptoms ● Mediastinal involvement: SOB, SVCO ● Spinal cord compression B symptoms (in advance disease) Alcohol induced LN pain, pruritus Ix CBC Excisional biopsy Staging Ann Arbor system Mx Stage I – II RT (localised): involved field ER ● S/E: second cancer, IHD, hypothyroid, lung fibrosis (Depending on field) +/- chemotherapy Advanced stage (III – IV, bulky II) Chemotherapy ● ABVD: Adriamycin, bleomycin, vinblastine, dacarbazine Consider autologous HCST ?+/- staging splenectomy

Answer 48

Presentation: Local: painless lymphadenopathy (B symptoms less frequent) Extranodal involvement: skin (Sezary), GIT lymphoma, Waldeyer’s ring, HPSmegaly Emergencies: SVCO, TLS, malignant hypercalcemia, pericardial effusion, IO, CNS Diagnostic: - excisional Bx of LN - Immunophenotyping (flow, IHC); clonality (IGH mutation, cytogenetics); molecular genetics - CBC D/C, PBS, DAT, TLS panel RFT + CaPO4 + urate, LDH, b2-microglobulin - LFT, ESR - IgG, IgA, IgM, SPE Pre-treatment - Hepatitis serology, TB, HIV, G6PD - ABVD: lung function test - Pregnancy test Staging: - BM aspiration & biopsy from bilateral iliac crest - PET-CT (DLBCL), LP if high risk CNS involvement Mx: - Limited stage Ann arbor I / II + no B symptoms + mass < 10cm: chemo + local RT - Advanged stage III/ IV OR B symptoms OR mass >10cm: extended chemo +/- RT Systemic chemotherapy R-CHOP + localized RT - Rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, prednisolone - Pre-treatment o R: Panadol + diphenhydramine premedication +/- H2 blocker (infusion reaction) o C: oral hydration + ↑voiding (hemorrhagic cystitis) o H: avoid extravasation, ECHO o O: neurotoxicity, paralytic ileus - Monitoring: CBC D/C, RFT LFT, LVEF Alternative: R-ICE; dose adjusted EPOCH-R (R CHOP E – etoposide) Alternative: pembrolizuma R-CHOP S/E ● R: Nausea, infection, infusion-related problems ● C: hemorrhagic cystitis, primary ovarian failure, alopecia, marrow ● H: cumulative cardiotoxicity; mucositis, myelosuppression, red urine ● O: peripheral neuropathy ● P: Cushing ● General: febrile neutropenia (10-20%) – consider prophylactic G-CSF Monoclonal Ab: anti-C20, anti-CD30 (HL), anti-CD52 Targeted Tx ● BTK inhibitor: ibrutinib (B cell lymphoma) ● BCL2 inhibitor: venetoclax (CLL, follicular lymphoma) ● ALK inhibitor: crizotinib (anaplastic LCL) Immunotherapy: bispecific T cell activator, PDL1 CAR-T cell HSCT

Answer 49

HCC, prostate CA, testicular cancer

Answer 50

Young man - lymphoma - germ cell tumour —> chemo sensitive Look for laryngioedema —> intubation Take biopsy first before give steroid since if lymphoma —> excisional biopsy is important for architecture —> steroid may destroy it and affect diagnosis Not goodly receive chemo - mediastinum —> give RT for lymphoma for possible residual disease - testis - CNS —> intrathecal - orbit Delayed toxicity - pneumonitis - infertility (chemo) - heart - secondary malignancy, e.g. leukemia after high dose chemo - CA thyroid Central-located mass: - SVCO - tamponade - RLN - airway —> lung collapse Peripheral-located - pleural effusion Superior sulcus (apical) (pancost tumour —> no SVCO since SVC already bifurcated) - Horner’s syndrome - T1 neuropathy —> brachial plexus - dermatomal shoulder pain

Answer 51

- check sensory level ** (MRI may give both old and new lesion) - MRI to confirm diagnosis —> collapse of vertebrae / loss of pedicle (not TB not malignancy) (unstable spine) —> need surgery for spinal fusion - but if radiosensitive like plasmacytoma —> RT first-line

Answer 52

- usually occur spontaneously (high risk malignancy) —> burkitt’s lymphoma —> high LDH, expand in size very quickly , common presentation: extra-nodal sites: GI tract (bowel perforation / IO —> present to surgery)

Answer 53

AML-M3 - give altra —> prevent DIC * most patient die for DIC in 1-2 weeks - then give chemo within 1 week DIC - fibrinogen decrease / increase - D-dimer increase (elevation may not mean must DIC, but DIC must increase d-dimer)

Answer 54

1. Known you have cancer —> what cancer —> when occur? 2. Treatment? Response? What doctor said? —> landmark of the cancer —> the earliest complaints can be vaguely asked 3. Current presenting symptoms —> for PE

Answer 55

Classification 1. Papillary - 85% - Young adults - Lymphatics spread 2. Follicular - 10-15% - Middle age (40-60) - haematogenous spread 3. Anaplastic - 1% - Old > 60 - Lymphatics and haematogenous spread 4. Medullary - 3% - Sporadic: >50y; Familial: < 30y - Lymphatics spread Other rarer types: lymphoma (require core biopsy), SCC, poorly differentiated CA Metastatic thyroid cancer • Renal cell carcinoma (MC) • Others: colorectal, lung, breast, uterine Risk factors • Female • Family history of thyroid cancer • Previous H&N irradiation e.g. childhood leukemia • Familial syndrome, e.g. FAP (papillary), MENII (MTC) • Hashimoto's thyroiditis (thyroid lymphoma), iodine deficiency (follicular CA) Note: Follicular adenoma is NOT a risk factor of follicular CA Clinical features • Palpable neck lumps • Rapidly enlarging lumps: pain, HOV, stridor • Multiple enlarged cervical LN

Answer 56

Investigations • Bloods: TFT (normal), CaPO4 (parathyroid function), thyroid Ab and thyroglobulin (tumor marker) • Thyroid USG: suspicious features (SHIT CME) • FNAC: Bethesda system • CT neck and chest: if locally advanced CA thyroid / bulky LN • Pre-op workup for MTC o Rule out familial disease (25%): FHx, 24h urine metanephrines, Ca & PTH o Tumour markers: calcitonin (metatstatic if >500), CEA o Workup for metastatic disease if calcitonin > 500: CT T+A+P & bone scan Staging of thyroid cancer • Differentiated thyroid cancers: age-dependent o Age <55: Stage I if M0, Stage II if M1, never Stage III/IV o Age ≥55: Up to Stage IVB • Anaplastic thyroid cancers: Stage IV automatically • T staging: o T1a: tumor ≤ 1cm o T1b: 1cm < tumor ≤ 2cm o T2: 2cm < tumor ≤ 4cm o T3: >4cm but limited to thyroid o T4: extrathyroidal extension • N staging: o N1a: Level VI / VII nodes o N1b: Level I-V node

Answer 57

1. Surgery - Papillary / follicular —> Total thyroidectomy Indications: size > 4cm, gross extra thyroidal extension, LN positive, metastasis positive, familial disease, bilateral/multifocal • Papillary CA tends to be multifocal • Prevent local recurrence which may progress • Allow post-op thyroglobulin monitoring • Allow adjuvant RAI —> Hemithyroidectomy • Morbidities are lower, especially parathyroid & RLN injury • Progression to undifferentiated CA is rare • No evidence to show inferior prognosis • Lifelong thyroxine replacement not required • RAI is not required in most patients - Medullary CA thyroid: total thyroidectomy (require prophylactic total thyroidectomy in high-risk MEN2 cases) Choice of neck dissection Terms: central compartment dissection (Level VI) vs lateral neck dissection (Level II-V) 1. Papillary CA thyroid: • Therapeutic CCD / LCD if respective compartment +ve • No role for prophylactic neck dissection 2. Follicular CA thyroid: • Usually not required (haematogenous spread) 3. Medullary CA thyroid: often need to dissect one level up • Prophylactic CCD for all patients • Ipsilateral central LN +ve: + ipsilateral LCD • Ipsilateral lateral LN +ve: + ipsilateral LCD (if calcitonin < 200), + bilateral LCD (if calcitonin > 200) • Contralateral LN +ve: +bilateral LCD Post-operative adjuvant treatments - Remnant ablation: o Residual thyroid tissue actually non-functional (require T4 supp anyway), but it interferes with post- op thyroglobulin monitoring and also cannot r/o residual malignancy! 1. Radioactive iodine ablation (RAI): - Pre-op give rTSH or withdraw T4 to promote 131I intake - Low iodine diet x1 week Similar to indication for total thyroidectomy (above): • T3 / T4 disease • N1 / M1 disease • Aggressive histology: tall cell, columnar cell, diffuse sclerosing, poorly differentiated PTC 2. External beam irradiation (EBRT) Indications include: • Positive surgical margins • Incomplete resection (residual tumor left) Thyroxine o Roles: Replacement (prevent hypothyroidism) ± suppression (high TSH stimulates tumour growth) - high risk: T4, M1/ incomplete resection —> TSH < 0.1mIU/L - intermediate risk: T3, N1, aggressive histology, vascular invasion positive —> 0.1-0.5 - low risk: others —> 0.5-2.0 Disease monitoring: o Neck USG Q6m - Bloods: TSH, calcium, PO4 & thyroglobulin (on thyroxine suppression) Q3m - can be performed for both total/ hemithyroidectomy • Total hemithyroidectomy: Tg < 0.2 • Hemithyroidectomy: Tg < 30 **thyroxine taken before breakfast and at least 1 hr apart from Ca+ since Ca+ affect thyroxine absorption

Answer 58

MEN1: Pituitary adenoma Parathyroid hyperplasia Pancreatic tumour MEN2a: Parathyroid hyperplasia Medullary thyroid carcinoma Pheochromocytoma MEN2b: Mucosal neuroma Mariano I’d body habitus Medullary thyroid carcinoma Pheochromocytoma

Clinical Oncology Flashcards

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