Case 17: gastric and complications Flashcards
1
Q
Investigations gastric cancer
A
- FBC, LFT
- diagnosis: endoscopy (gastroscopy) with biopsy
- staging: CT or endoscopic ultrasound - endoscopic ultrasound has recently been shown to be superior to CT
- Diffuse gastric cancer on biopsy: signet ring cells
2
Q
Staging: gastric caner
A
- CT scanning of the chest abdomen and pelvis is the routine first line staging investigation in most centres.
- Laparoscopy to identify occult peritoneal disease
- PET CT (particularly for junctional tumours)
3
Q
Surgery: gastric cancer
A
- Partial gastrectomy: Removal of a portion of the stomach, suitable for early-stage, localized tumours
- Total gastrectomy: Removal of the entire stomach, often necessary for larger or more advanced tumours
- Lymph node dissection (D1 or D2) should be performed according to tumour stage and location. Minimally invasive techniques, such as laparoscopic or robotic-assisted surgery, may be considered for selected cases.
4
Q
Indications for different types of gastrectomy and curative treatment for gastric cancer
A
- Total: tumour is proximal
- Subtotal: if tumour is antral or treatment is palliative, especially if obstructing
Curative treatment of gastric cancer: gastrectomy plus lymphadenectomy with chemo pre/post op
5
Q
Chemotherapy gastric cancer
A
- Neoadjuvant chemotherapy: Administered before surgery to shrink the tumour and improve resectability +/- radiotherapy
- Adjuvant chemotherapy: Given after surgery to eradicate residual disease and decrease the risk of recurrence +/- radiotherapy
- Palliative chemotherapy: for metastatic or unresectable disease to control symptoms and prolong survival +/- radiotherapy
- Common chemotherapeutic agents include fluoropyrimidines (e.g., 5-fluorouracil, capecitabine), platinum compounds (e.g., cisplatin, oxaliplatin), and taxanes (e.g., paclitaxel, docetaxel).
6
Q
Targeted therapy: gastric cancer
A
- Anti-HER2 therapy (e.g., trastuzumab, pertuzumab): Effective for HER2-positive tumours, used in combination with chemotherapy
- Anti-VEGF therapy (e.g., ramucirumab): Targets vascular endothelial growth factor, employed for advanced or metastatic disease
- Immune checkpoint inhibitors (e.g., pembrolizumab, nivolumab): Effective in some cases of microsatellite instability-high (MSI-H) or PD-L1-positive tumours
7
Q
Supportive and Palliative are in gastric cancer
A
- Nutritional supplementation, pain management, psychological support
- Consider subtotal gastrectomy, chemo
- endoscopic pyloric stent (plastic tube through tumour)
- PPIs for bleeding, ulcerating tumours
8
Q
Gastric cancer complications
A
- Obstruction: vomiting, malnutrition,dehydration
- Perforation, Peritonitis and sepsis
- Metastasis to the liver, lungs and peritoneam
9
Q
What can cause lymphadenopahty in the supraclavicilur fossa or axilla
A
What can cause lymphadenopathy in the supraclavicular fossa or axilla: breast, lung, oesophagus and stomach.
Most common caner type found in lymph nodes with unknown primary: adenocarcinoma
10
Q
How do carcinomas of unknown primary present
A
- clinical absence of primary tumour
- often multiple sites of involvement
- unpredictable metastatic pattern
- greater aggressiveness
- Median age: 60
- % of cancer which are from an unknown primary: 4.5%
- Median survival: 6-9 months
11
Q
Poor prognostic factors for carcinoma of unknown primary
A
- number of metastatic sites
- male
- poor performance status
- weight loss more than 10%l
- lymph node involvement other than supraclavicular fossa
- Investigation in unknown primary- biopsy lymph node
12
Q
Chemosensitive and hormone sensitive tumours
A
- Chemosensitive tumour: Non-Hodgkin’s lymphoma, Germ cell tumours, Neuroendocrine tumours including Small Cell Lung Cancer, Ovarian cancer
- Hormone sensitive tumour: Breast cancer, Prostate cancer, Endometrial cancer, Thyroid cancer
13
Q
5 different causes of unknown primary resulting in squamous cell carcinoma of the cervical nodes
A
- Breast cancer: women with isolated axillary lymphadenopathy often have an occult breast primary
- Primary peritoneal cancer: papillary carcinoma with elevated CA-125, laparotomy fails to identify a primary. Treat like stage III ovarian cancer
- Extragonadal germ cell tumours: in young men with pulmonary or lymph node metastases and germ cell tumour markers (AFP and HCG). Cytogenetic analysis will be positive for isochromosome 12p
- Neuroendocrine tumour: histologically poorly differentiated. Stains are positive for chronogranin or NSE. Often have diffuse hepatic or bone metastasis
- Head and neck tumours: treat with radical neck dissection and extended field radiotherapy
14
Q
Investigations for squamous cell carcinoma in lymph nodes
A
- Meticulous inspection of scalp and skin for primary tumour
- Ear nose and throat examination, indirect laryngoscopy ± examination under anaesthesia (EUA) with blind biopsies from nasopharynx & base of tongue
- CT of chest/abdomen/pelvis (lung, cervix)
- Upper GI endoscopy (oesophageal and gastric)
- Colposcopy and cervical smear
15
Q
Treatment for squamous cell carcinoma in cervical lymph nodes
A
- Aggressive local therapy to the neck: radical neck surgery, high dose radiotherapy or a combination
- Chemotherapy with cisplatin and 5-FU can improve response
16
Q
Investigations for anaplastic carcinoma in cervical nodes
A
- CXR; sputum cytology (most reliable in small cell lung cancer)
- Thyroid scan + needle biopsy
- Nasopharyngeal assessment
- Consider diagnosis of undifferentiated lymphoma (exclude with immunophenotyping)
17
Q
Investigations for squamous cell carcinoma in inguinal nodes
A
- Careful examination of legs, vulva, penis, perineum for primary tumour
- Pelvic examination (exclude vaginal/cervical cancer)
- Proctoscopy/colposcopy (exclude anal/cervical cancer)
18
Q
Investigations for metastatic adenocarcinoma
A
- Oestrogen receptor (ER) and progesterone receptor (PR) expression by tumour in females
- Serum prostate specific antigen (PSA) and acid phosphatase in males
- Serum alpha fetoprotein (AFP) and human chorionic gonadotrophin (HCG) (if positive, histology needs review)
- Consider diagnosis of poorly differentiated lymphoma, exclude with immunophenotyping
- Adenocarcinomas in higher nodes and patients with lower lymphadenopathy f any histology have poorer prognosis. Managed with local (radiation therapy)
19
Q
Unknown primary tumour: areas involved and treatment
A
- Majority do not have a determined cause and response rate to chemo is <20%
- 2/3rds of unknown primary cancer have metastatic adenocarcinoma with involvement of two or more visceral sites, including liver, lung, lymph nodes, or bone
- Treat with empirical systemic chemotherapy based on adriamycin, 5-FU or cisplatin. Little response
- No treatment for metastatic adenocarcinoma in >2 sites
20
Q
Histological cause of unknown primary
A
60% are adenocarcinoma, 30% poorly differentiated carcinoma, 5% poorly differentiated neoplasm, 5% squamous cell carcinoma
21
Q
Histological analysis of unknown primary
A
- Light microscopy
- Immunocytochemical staining
- Surface immunophenotype: done through immunohistochemical/immunofluorescent staining or flow cytometry
- Electron microscopy: can visualise intracellular features
- Molecular analysis: can see translocations and gene amplifications
22
Q
Light microscopy results for different unknown primaries
A
- Signet ring cells (favour gastric primary)
- Presence of melanin (favour melanoma)
- Presence of mucin is common in gut/lung/breast/endometrial cancers, less common in ovarian cancer and rare in renal cell or thyroid cancers
- Presence of Psammoma bodies (calcospherites) is a feature of ovarian cancer (mucin positive) and thyroid cancer (mucin negative)
23
Q
Electron microscope: different cancers
A
- Melanoma: Melanosomes
- Neuroendodermal tumours: Dense core granules
- Adenocarcinoma: intracellular lumina and surface micorvilli
- Squamous tumours: desmosomes and prekeratin filaments
- Carcinoids: Neurosecretory granules
24
Q
Patients with unknown primary definition
A
a biopsy-proven malignancy, where the anatomic origin remains unidentified after history and physical examination including laboratory studies
25
Investigations for patients with unknown primary: depends on cause
- Physical examination: careful palpation of the thyroid, breast, lymph node, testicle, bimanual, liver and prostate.
- Bedside: PR exam, FIT
- Bloods: FBC, U&E, LFT
- CXR, CT TAP (thorax, abdomen and pelvis), Mammography
- Other: sputum cytology, CT chest, breast US or GI endoscopy
26
How unknown primary presents
- Distant metastasis and lymph node involvement without any primary cancer
- Supraclavicular lymph nodes with squamous cell carcinoma have poor prognosis
- Common sites involved: Lung, bone, lymph node and liver
27
Symptoms of Hypercalcaemia of malignancy
- pruritus, lethargy and fatigue
- Rapid onset nausea, polyuria, polydipsia, dehydration, cardiac arrhythmia’s, costipatin
- ‘bones, stones, groans and psychic moans’
- Corneal calcification
- Shortened QT interval on ECG
- Hypertension
- Dehydration, Cardiac arrhythmias
28
Different causes of Hypercalcaemia of malignancy
- THrP from the tumour e.g. squamous cell lung cancer. Caused by squamous cell carcinomas in different areas
- Due to PTH-rP: NSCLC, Head and Neck, Renal, SCC of oesophagus or cervix. Rare in breast cancer, more commonly due to bone metastasis
- bone metastases
- myeloma: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells
29
Hypercalcaemia management
- Rehydration with normal saline 3-4 litres/day
- Post rehydration use Bisphosphonates (maximal effects at 7 days)
- Calcitonin: quicker effect than bisphosphonates
30
Metastatic Hypercalcaemia due to protein production
- True paraneoplastic hypercalcaemia is due to tumour production of parathyroid hormone-related protein
- PTH-rP produces hypercalcaemia of malignancy without bone metastasis
- It is 100-fold more potent than PTH
- 10% of patients with cancer develop hypercalcaemia
31
Paraneoplatic syndrome definition
The clinical manifestations of a non metastatic manifestations of an underlying cancer
32
Hypercalcaemia of malignancy diagnosis
Serum Ca2+ > 2.7 mmol/l, serum chloride low, hypercalcuria, high urinary phosphate, low or undetectable plasma parathyroid hormone
33
Paraneoplastic syndrome
- Tumours can produce signs and symptoms at sites distant from the primary tumour or its metastases. Not a direct result of the cancer
- This can be due to substances produces by the tumour causing distant symptoms, depletion of normal substances or host response to the tumour (immunological)
- May be the first sign of malignancy. Some paraneoplastic proteins are used as tumour markers. Paraneoplastic symptoms can be more distressing then the cancer
- Range of symptoms include: Endocrine, Haematological, GI, Renal, Cutaneous, Neurological
34
Endocrine manifestation of Paraneoplastic syndrome: ACTH
- Patients with ectopic ACTH syndrome have a much higher ratio of ACTH precursors to endogenous ACTH
- Overproduction of ACTH precursors: ACTH and MSH, b-lipotropin, endorphins, encephalins, propiomelanocortin (POMC)
- Cancer types: SCLC (50% of cases of ectopic ACTH), NSCLC, pancreatic, thymic and carcinoid tumours, phaemochromocytoma, medullary carcinomaof the thyroid
- Rapid onset
- May develop Cushing’s syndrome: Truncal obesity, hypertension, fatigue, depression, weakness, hirsutism, hypokalaemia, metabolic alkalosis, hyperpigmentation, oedema, diabetes millitus
35
Ectopic ACTH: diagnosis and treatment
- Diagnosis: Clinical features, esp. hyperpigmentation, marked weakness secondary to proximal myopathy. Metabolic disturbances i.e. hypoglycaemia, hypokalaemia and metabolic alkalosis; high 24hr urinary cortisol, high plasma ACTH/precursors, no response to high-dose dexamethasone suppression or corticotropin-releasing hormone stimulation
- Treatment: Specific anti-tumour treatment. Decrease cortisol secretion either surgically (bilateral adrenalectomy) or medically (octreotide, ketoconazole, aminogluthethamide)
36
Paraneoplatic syndrome inappropriate diuresis
- The most common endocrine paraneoplastic syndrome, due to inappropriate secretion of ADH
- Results in SIADH
- Causes are normally pulmonary, CNS, drugs
- Cancer types: SCLC, pancreatic, prostate, NHL, HD
- Presentation: often asymptomatic, CNS toxicity (fatigue,headache, progressing to altered mental state, confusion and seizures)
- Diagnosis: exclude non malignant causes, pulmonary disease and drug induced
- Treatment: fluid restriction (0.5-1L/day), democlocycline
37
Laboratory criteria for diagnosis of SIAD
- Hyponatremia Na+ <130 mmol/L
- Normal serum albumin and glucose
- Serum hypo-osmolarity <275 mosm/Kg
- Urine osmolarity > serum osmolarity
- Urinary sodium >25mmol/L
- Non-suppressed ADH
38
Paraneoplastic syndrome: Gonadotrophins
- Causes raised b-hCG, causes gynaecomastia in men
- Investigations: testicular exam, CXR/CT scan- exclude lung cancer
- Secretions occur in pituitary tumours, gestational trophoblastic tumours (women), germ cell tumours, hepatoblastomas in children and lung tumours
- Extragonadal tumours which secrete b-hCG: lung, adrenal, Hepatoma, GI tract tumours, GU tumours
39
Encephalomyopathies
- Due to antibodies generates against tumour antigens
- Perivascular inflammation and neuronal degeneration at several levels of the nervous system
- Can affect the limbic system, brainstem and spinal cord. Loss of neurons in the amygdala, hippocampus and insular cortex gliosis, lymphocyte cuffing of blood vessels, microglial nodules
- Cancer types: SCLC (75% of cases), breast, ovary, NHL
40
Encephalomyopathies: presentation, diagnosis, treatent
- Presentation: Slow, subacute onset; progressive, loss of short term memory, hallucinations, fits, personality changes
- Diagnosis: LP- CSF (raised protein/IgG level, pleocytosis), Serum (anti-Hu antibody), MRI
- Treatment: Anti-tumour therapy (cure cancer). Sometimes even when cancer is treated symptoms persist.
41
Lambert-Eaton myasthenic syndrome
- Disorder of the neuromuscular junction; reduced pre-synaptic calcium-dependent acetylcholine release
- Similar symptoms to Graves disease
- About 60% of patients have underlying cancer
- Cancer types: SCLC (60-70%), breast, thymus, GIT cancers
- Presentation: Proximal muscle weakness, Classical myaesthenia gravis affects bulbar muscles; LEMS does not, yet 30% will have dysphagia
42
Diagnosis and treatment of LEMS
- Diagnosis: EMG: normal conduction velocity with low amplitude compound muscle action potential that enhance to near normal following exercise
- Treatment: Cancer treatment, corticosteroids, plasma exchange (high response rate), cholinesterase inhibitors usually ineffective
43
Paraneoplatic syndrome: Dermatomyositis/polymyositis
- Inflammatory myopathies, often present prior to cancer diagnosis
- Cancer types: NSCLC, SCLC, breast, ovary, GIT cancers, associated with cancer in only 10% of cases
- Presentation: proximal myopathy, skin changes, other systemic features: cardiopulmonary conditions, arthralgias, retinopathy
- Skin: heliotrope salmon pink rash surrounding the eyes. Gottron’s papules on the extensor surface of joints, ancanthon nigrans
- 40% of people with Dermatomyositis have an underlying cancer
44
Parenoplastic syndrome: Dermatomyositis diagnosis and treatment
- Diagnosis: Serum: (high CK, LDH, aldolase). Muscle biopsy (myositis and inflammatory degeneration) EMG (fibrillation, insertion irritability, short polyphasic motor units)
- Treatment: Search for and treat tumour; corticosteroids, azathioprine, inconsistent course, independent of tumour
- Progression of skin condition can correlate to cancer course
45
Paraneoplastic syndrome: Haematological manifestations
- Erythrocytosis: can cause polycythaemia
- Anaemia
- Granulocytosis/granulocytopenia
- Thrombocytosis/thrombocytopenia: increased due to inflammation, decreased due to bone marrow infiltration
- Thrombophlebitis
- Coagulopathies and disseminated intravascular coagulation
- Nonbacterial thrombotic endocarditis
46
Types of lung cancer
- Small cell lung cancer (20%)
- Non small cell lung cancer (80%)
- Non small cell lung cancer can be split into: Adenocarcinoma (40%), squamous cell carcinoma (20%), Large cell carcinoma (10%)
47
Small cell lung cancer
- Arise in large airways, tend to be more central. Associated withsmoking
- Present with systemic disease and frequently metastasises via haematogenous routes to the liver, skeleton, bone marrow, brain and adrenal glands
- Can cause Cushing’s syndrome (ACTH) and SIAD
- 80% have mutations in RB1 and TP53
48
Non small cell lung cancer
- Arise from epithelial cells from the central bronchi to the terminal alveoli
- Squamous cell carcinoma: obstructive lesion of the bronchus causing infection. Grow slowly, spread locally and disseminate late. Can cause cavitating lesions. Associated with smoking
- Adenocarcinoma: arise from the bronchial mucosal gland and occur in the periphery. High risk of metastasis, originate in scar tissue. Most common in non-smokers
- Large cell carcinoma: present as a large peripheral mass on x-ray. Have paraneoplastic features. Poorly differentiated, grow rapidly and metastasise early
49
Lung cancer epidemiology
- Lung cancer is the most common malignant solid tumour in the UK
- Smoking is most commonly associated with SCLC
- 60-70 year old males
50
Lung cancer spread
spreads to ipsilateral peri bronchial and hilar nodes followed by mediastinal, contralateral hilar and supraclavicular nodes
