Cancer

NHS waiting rules for cancer

"2 week rule" if the GP suspects cancer, that patient has to be seen within 2 weeks "31 day rule" primary treatment must start within 31 days of agreeing a treatment plan with the patient "62 day rule" for patients under the 2 week rule, from the moment of referral, they must receive their first definitive treatment within 62 days of the referral If the trust breaches these rules, financial penalties are approximately 1/3 of a consultant's yearly salary

Complications of ovarian cancer

1) Local invasion Lymphedema Vaginal discharge Bowel obstruction Ascites*, pleural effusion 2) Metastasis Liver, lung, bone, brain 3) Non-metastatic PE Dermatomyositis** *Ascites at initial diagnosis can indicate better prognosis USS, MRI or CT can help guide drainage but diagnosis is usually clinical About 10% of patients with ascites have an underlying malignancy which is usually advanced Usually treated with paracentesis, medical treatment has not proven useful **Can present due to NSCLC, SCLC, breast, ovarian and GI cancers 10% of patients with dermatomyositis have an underlying malignancy Presents with proximal myopathy, skin changes, cardiopulmonary conditions, arthralgia and retinopathy Tests show high creatinine kinase, LDH, aldolase, myositis and inflammatory degeneration on muscle biopsy, fibrillation on EMG Treated by targeting the tumor and giving corticosteroids and azathioprine

Differentials and metastases for testicular cancer

A differential diagnosis of testicular cancer should include: orchitis, epididymo-orchitis, lymphoma and leukemia (biopsies will differentiate these). Metastases can occur in the lungs, brain, liver or lymph system.

Invasion of germ cell tumors

A seminoma is much more likely to spread through the lymphatics and is highly predictable. NSGCT spread through the lymphatics is comparatively unpredictable, but its spread through the blood is predictable (usually the lungs).

Lung cancer symptoms

A small proportion of patients will have no symptoms, but most will present with lung symptoms (cough, dyspnea, chest pain, hemoptysis, recurrent chest infections). The most common symptom is a cough, which occurs in 80% of cases, followed by hemoptysis, dyspnea, chest pain, anorexia and weight loss, swollen lymph nodes, palpable masses and lung collapse or pleural effusion. There can also be symptoms of infiltration.

AFP in germ cell tumors

AFP is elevated in 80% of non-seminomatous germ cell tumors. It is present in normal people at low levels and can be elevated in GI cancers, non-malignant liver disease and alcoholics (false positive with alcohol). It is significantly elevated in germ cell tumors and hepatocellular carcinomas. It has a longer half-life so it might remain elevated some time after cancer treatment. Embryonal and yolk sac carcinomas (NSGCT) almost always secrete AFP.

Lung cancer types

About 95% of all primary lung tumors are bronchial carcinomas (adenocarcinoma in situ). Bronchial carcinomas are the most common malignant tumor. Lung cancers are divided into small cell and non-small cell cancers. Non-small cell cancers are the most common, making up 85% of lung cancers, of which the most common is an adenocarcinoma. Some less common causes of lung cancer are mesotheliomas and metastases from colorectal, breast, ovarian, gastric or skin cancers. Mesothelioma is more common with asbestos poisoning. Mesothelioma is a consequence of asbestosis or asbestos exposure. Pulmonary fibrosis can progress to an adenocarcinoma. Small-cell cancers are highly malignant.

Cancer of unknown primary (CUP)

Also known as adenocarcinoma of uncertain origin (AUO) or occult primary malignancy. It is a unique entity where a primary tumor is able to metastasize before the primary site becomes large enough to be detected. It is different to cancers that have a known primary because it disseminates early, has an unpredictable metastatic pattern and a clinical absence of a primary tumor. They tend to be very aggressive and sometimes asymptomatic. About 2.3-4.5% of all cancers are from an unknown primary. It is the 4th most common cause of cancer death in both sexes. 50% of patients will present with multiple sites of involvement. The average age of presentation is 60. Even at post-mortem, 70% of cancers cannot be identified. The most common sources are the lung, GI tract and gynecological locations. For some cancers, earlier detection is very important (ie. Testicular, which is treatable) while for others it does not make a difference (ie. Pancreatic, has a bad prognosis anyway)

BRCA inheritance

BRCA gene mutations are almost always heterozygous and are inherited in an autosomal dominant fashion. As such, having one parent with the mutation results in a 50% chance of that gene being passed on to a child.

Beta HCG in germ cell tumors

Beta-HCG is a glycoprotein that is elevated in germ cell tumors and gestational trophoblastic disease. Its sensitivity is 50-80% in germ cell tumors, 15% in seminomas and 100% in testicular or placental choriocarcinomas. Cannabis use can sometimes give a false positive. Seminomas secrete beta-HCG but not other tumor markers.

Imaging for germ cell tumors

Bilateral ultrasound scan and CXR are used pre-operatively

Investigation of lung cancer

Biopsies Chest x-rays CT scans Bronchoscopy Trans-thoracic needle biopsy (best investigation, most accurate) Percutaneous fine needle aspiration Bone scan to look for metastases Sputum cytology (easy to get false negatives) All patients need to have a chest x-ray, FBC and biochemical profile (U&Es, LFTs, LDH and serum calcium). Patients with non small cell lung cancers should have imaging of the upper abdomen because it is common to have metastases in the liver and adrenal glands. It is therefore common to do both a contrast CT scan of the thorax and upper abdomen. For patients with non-small lung cell cancer, if you are considering radical treatment (ie. Removal of lung), they require pulmonary function tests to see if they have enough reserve function to handle the removal of the lung. You can also consider a CT, V/Q scan, MRI, USS and PET-CT.

Breast cancer overview

Breast cancer is the most common cancer after non-melanoma skin cancers. The lifetime risk is 1 in 9 and it is the commonest cause of death in women 35-54. The incidence is increasing. 80% of patients are alive and disease-free after five years. It follows an unpredictable course with some metastases presenting up to 20 years after initial diagnosis.

Tumor markers in ovarian cancer

CA-125 can be secreted by many tissues, but not from normal ovaries It is made by anything that causes inflammation, infection or infarction (appendicitis, pleural effusion) It is present on the cell surface of >80% of non-mucinous ovarian tumors High levels are associated with poor prognosis (except in stage 1 disease with level >65) A rise >25% is the most accurate method of predicting progression A doubling from the upper limit of normal during follow-up predicts relapse with 100% specificity There is no impact on survival of early treatment based on CA-125 elevation Other markers also have a role: breast mucins (CASA, OVX1 and HMFG2), cytokeratin proliferation markers, AFP and beta HCG but none of these are as useful as CA-125

BRCA1 vs BRCA2

Cancers associate with BRCA1 and BRCA2 - Breast cancer (patients tend to be younger in BRCA1) - Ovarian cancer - risk is higher with BRCA1 mutation than BRCA2 - Male breast cancers (risk higher with BRCA2) - Pancreas - risk higher with BRCA2 mutation than BRCA1 - Prostate - risk higher with BRCA2 mutation than BRCA1 Other cancers associated with BRCA1 - ?Colon Other cancers associated with BRCA2 - Stomach - Gallbladder/bile duct - Melanoma

10 hallmarks of cancer

Cancers... 1) Control their own proliferation by producing growth signals themselves or by having overactive signal receptors 2) Are insensitive to signals that stop cell division as a result of mutations or alterations to tumor suppressor genes 3) Resist cell death (apoptosis) due to mutations in tumor suppressor genes 4) Have limitless ability to divide because they activate telomerase 5) Create their own blood supply through angiogenesis 6) Can invade other organs by entering the newly formed blood vessels it created 7) Are able to survive with little oxygen due to anaerobic respiration 8) Evade the immune system through complex and poorly understood processes 9) Accumulate genetic mutations that promote self proliferation (ie. Activating oncogenes) or disrupt control (ie. Deactivating tumor suppressor genes) 10) Thrive in chronic inflammation that promotes proliferation, cell survival and angiogenesis, as well as producing free radicals that can damage DNA

Ectopic ACTH in lung cancer

Ectopic ACTH causing Cushing's (truncal obesity, hypertension, fatigue, weakness, hirsutism, hypokalemia, metabolic alkalosis, hyperpigmentation) Mostly in small cell lung cancers (50% of cases) followed by NSCLC, pancreatic, thymic, pheochromocytoma and thyroid cancer Rapid onset of weakness and proximal myopathy, hyper-pigmentation, metabolic disturbance (ie. Hyperglycemia, hypokalemia) Diagnosed by looking at clinical features (especially hyperpigmentation, myopathy) and tests (hypokalemia, metabolic alkalosis, urinary cortisol, dexamethasone suppression) Main treatment is to remove the cancer but it can be reduced with an adrenalectomy or medically with ocrteotide, ketoconazole or aminogluthethamide

Li-Fraumeni syndrome

Germline mutation of one TP53 gene (chromosome 17p). Li Fraumeni syndrome is characterized by premenopausal breast cancer, childhood sarcoma, brain tumors, leukemia and lymphoma, and adrenocortical carcinoma. Inheritance is autosomal dominant with a penetrance of at least 50% by the age of 50. TP53 causes cell apoptosis and allow for DNA repair. A cancer with a defect in TP53 will not stop to allow repair, it will continue dividing. Most cancers will show a loss of TP53 suppression. Carboplatin is a drug that works by inducing apoptosis, so you cannot give carboplatin to patients who have cancer that is defective in TP53 because the apoptosis will not happen.

Gonadotrophin secretion in lung cancer

Gonadotrophins can be secreted in some tumors (pituitary, gestational, trophoblastic, germ cell, hepatoblastomas and lung) and the signs are associated with raised beta HCG, it is usually seen as gynecomastia in men

Clinical signs of lung cancer

Hands: nicotine staining, clubbing Neck: lymphadenopathy Chest: pulmonary collapse or consolidation Pancoast's syndrome (chest wall pain, Horner's syndrome and pain in the T1 distribution due to the tumor invading the chest wall and interrupting the sympathetic chain) Hematological: anemia Neuromuscular: Lambert-Eaton syndrome Cutaneous: Acanthosis nigricans (due to ectopic hormone production ie. High calcium)

Investigations for ovarian cancer

History and examination Bloods FBC Serum biochemistry LFTs Bone profile TFTs (some rare ovarian cancers can produce thyroid hormone) Tumor markers Exploratory laparotomy in order to de-bulk the tumor and stage the disease Imaging - Ultrasound - CT and MRI not helpful in diagnosis but can provide pre-operative assessment Endometrial sampling if abnormal PV bleed Pre-operative cytological and histological evaluation of effusions or masses Paracentesis or needle biopsy are not used because they can seed tumor cells and delay managementTU

Symptoms of ovarian cancer

Insidious and asymptomatic, can grow to 10-12cm before producing symptoms Abdominal distension (bloating, swelling, ascites), GI symptoms (loss of appetite, nausea, vomiting, constipation, abdominal pain) Urinary frequency, rectal pressure, hydronephrosis secondary to ureteric obstruction, hematuria, recurrent UTI, loin pain, renal failure PV bleed (rare) Pelvic mass on routine pelvic examination Fatigue, anorexia Advanced disease is also usually asymptomatic, but can lead to ascites, indigestion, back ache Some patients with advanced cancer can have normal-sized ovaries Pleural effusion (breathlessness) Woman are educated to watch out for the following symptoms: persistent pelvic and abdominal pain, increase in abdominal size or persistent bloating, and difficulty eating or feeling full quickly

Risks for ovarian cancer

It is associated with incessant ovulation (low parity, ovulation inducing drugs), infertility and patients with family history of cancer. BRCA 1 gene (50% lifetime risk) and two other mutations called Lynch 2 syndrome (12% lifetime risk) increase the likelihood. These patients may undergo a prophylactic salpingo-oopherectomy. Oral contraceptives have a protective effect because they stop ovulation. Talc (hydrous magnesium trisilicate, used on sanitary napkins), radiation and diet (fat, lactose, coffee) have been shown to have some connection. BRCA mutations are inherited in an autosomal dominant fashion. BRCA1 is a tumor suppressor and protects DNA against oxidative damage. Jewish women of eastern European descent have a 1 in 100 prevalence of BRCA1 mutations. BRCA1 mutations increase the risk of both breast and ovarian cancers (90% for breast and 65% for ovarian). Some ovarian cancers can also be related to BRCA2 or HNPCC mutations.

Investigations for germ cell tumors

It is investigated with tumor markers, scrotal ultrasound and imaging (essential for staging and is often performed after an orchidectomy). In the context of a testicular mass, a rise in beta-HCG or alpha-fetoprotein (AFP) strongly suggests a malignancy, they can be diagnostic and prognostic (if they are high, the prognosis is worse). They are also used for surveillance (looking for a reduction -- if the tumor is removed and the markers go up, this tells you the disease was not removed successfully). Seminomas secrete beta-HCG but not other tumor markers. Embryonal and yolk sac carcinomas (NSGCT) almost always secrete AFP. Lactate dehydrogenase (LDH) indicates necrosis and is therefore associated with tumors that grow rapidly, but it is non-specific Serum markers need to be measured before and 24 hours after orchidectomy (then weekly until normal), hCG should normalize within 24 hours and AFP in 4-6 days

Breast cancer investigations

It is recommended to begin breast self-examination at age of 20, but few (2-3%) due the examination properly. Masses are examined with fine-needle aspiration (FNA), ultrasonography (USS) and biopsy.

Management of lung cancer

It is treated surgically and through chemotherapy and radiotherapy. Patients can receive endobronchial therapy (stents to open the airways), laser therapy, cryotherapy and oxygen. Complications of cancer therapy include: Chemotherapy: neutropenic sepsis, anemia Radiation: pneumonitis, toxicity to normal tissue Surgery: reduced exercise tolerance

Leptomeningeal metastasis

Leptomeningeal metastasis (infiltration of meninges), brain metastases are more common now because patients are living longer with lung cancer which gives the cancer a chance to spread, they occur in one of the hemispheres (80%), cerebellum (15%) and leptomeningeal (5%); these patients present with headache (70-80%), cognitive dysfunction (40%), neurological deficit (40%) and seizures (15-20%); treatment is supportive (steroids, anticonvulsants) or definitive (surgery, radiotherapy, chemotherapy) Steroids are useful because they can predict who will respond to radiotherapy Sodium valproate is the most common anticonvulsant used Surgery is useful if there is a solitary site of metastasis Radiotherapy is not as useful and most chemotherapy agents don't cross the blood brain barrier It is possible to get metastases in the skin, particularly with NSCLC and SCLC. This is automatically stage IV disease. It can be treated with radiotherapy or chemotherapy.

Complications of breast cancer

Local invasion (lymphedema, pleural effusion, ascites) Distant metastasis (bone, liver, lung, brain, spinal cord compression) Hypercalcemia

Lung cancer overview

Lung cancer is the most common malignant solid tumor in the UK (excluding non-melanoma skin cancer) and approximately 7% of patients are alive and disease free after 5 years, meaning the prognosis is poor. The peak incidence is at 60-70 years and the incidence is higher than the prevalence (more patients are diagnosed than alive at any given time). It is more common in men, but male incidence is decreasing while female incidence is increasing. Lung cancer spreads locally through lung tissue and the regional lymphatics (ipsilateral peri-bronchial and hilar nodes, followed by the mediastinal, contralateral hilar and supraclavicular nodes). It starts with the lymph nodes on the same side of the chest before moving to the opposite side and then finally invading the bloodstream. This leads to bone, liver and brain metastases. You do not need to know the staging classifications but know that the staging is based on the location of the cancer at diagnosis.

Sites of metastasis for lung cancer

Lung cancer often metastizes to the brain, bone, liver and adrenal glands.

Management of germ cell tumors

Management of early cancers is surgical (orchidectomy with inguinal approach) even if the diagnosis is uncertain. The contralateral testis should be biopsied if small (<12mL) or the patient is <30 years old. Testicular prosthesis can be offered afterwards.

Risk factors for breast cancer

More common in white women with a higher socioeconomic background More common in left breast Family history (particularly if young at diagnosis or in males with breast cancer, any cancer history -- not just breast) Early menarche and late menopause Nulliparity or late first pregnancy (>35) Estrogen therapy (OCP/HRT) Radiation Obesity Alcohol The overall risk of breast cancer in a woman with a positive family history is 1.7. Genes associated with breast cancer include BRCA1, BRCA2, P53 (Li-Fraumeni syndrome), Cowden syndrome (breast and GI cancer, thyroid disease), ataxia telangiectasia and Peutz-Jegher syndrome. BRCA-associated disease will tend to present at a younger age, often bilaterally with worse histological features. They also tend to present with multiple cancers (ie. Breast and ovarian). Nearly all male patients with breast cancer will have a BRCA2 mutation.

Types of ovarian cancers

Most ovarian tumors (90%) are of epithelial origin and have five categories: serous (majority), mucinous, endometrioid, clear cell (rare and aggressive, CA-125 often not raised) and transitional cell (rare). Non-epithelial types include sex cord stromal tumors, sarcomas and germ cell tumors.

Breast cancer symptoms

Most patients are asymptomatic and found on screening or they present with a lump. Some present with Paget's disease (associated with intra-ductal carcinoma which presents as eczema on the nipple, breast mass or bloody discharge). Other symptoms include breast pain (5%), breast enlargement (1%), skin or nipple retraction (5%), nipple discharge (2%) and nipple crusting or erosion (1%). Clinical signs include neck lymphadenopathy, nipple discharge or retraction, breast discoloration, edema, Peau D'Orange, erythema, nodules, ulceration, asymmetry, skin thickening, chest consolidation, hepatomegaly, focal tenderness in muscles and distant metastases (bone 70%, lung 60%, liver 55%, pleura 40%, adrenals 35%, skin 30% and brain 10-20%).

Bone metastases

Most people who die of cancer have metastases and the bone is the third most common organ involved in metastasis. 90% of patients who die of breast cancer have bone metastasis. Breast and prostate cancers metastasize to the bone most frequently, followed by kidney, thyroid and multiple myeloma. There is an average 2 year survival from the time of presentation of a bone lesion. It is managed conservatively (ie. Pain relief). MRI is the investigation of choice for spinal compression, about 70% are thoracic and 15% are lumbar. If a patient presents with cervical compression above C5, this will interrupt respiration and many patients stop breathing and die. Any bilateral upper motor neuron signs should be considered spinal cord compression until proven otherwise. A bone radio-isotope scan can be done for bone metastases. Breast cancer is also the second most common cause of brain metastasis (15-20%, after 50% being lung). It can lead to leptomeningeal metastasis. This is treated with intra-thecal radiotherapy.

Neutropenic sepsis

Neutropenic sepsis is a serious condition that is characterized by a fever of >38 on one reading or >37.5 on two readings over an hour, rigors, unexplained hypotension or tachycardia and a neutrophil count <1x10^9. The neutropenia is usually secondary to chemotherapy but can also occur with radiotherapy. The risk of an infection depends on the degree of neutropenia and bacterial access (ie. Catheter). Initial management is to screen for sepsis (take cultures from wherever you can) and commence antibiotics immediately. Currently the guideline is to give tazocin and gentamicin. Neutropenic sepsis is the leading cause of chemotherapy-related death and the mortality rate rises to 80% after 40 hours so antibiotics need to be commenced as soon as possible. Paracetamol and PV/PR exams should be avoided (risk of disseminating sepsis) and prognosis is worsened if there is diarrhea, hypotension, coagulopathy or organ failure.

How patients with CUP present

Patients with cancer can present through: Screening (breast, cervical, potentially prostate and colorectal to be introduced) Age (40% of patients >75 have their cancer diagnosed in the emergency department) Symptoms (resent onset or change in symptoms, discovery of a lump) Patients may not present due to: Awareness (education, media, personal experience) Symptoms (patients choose to put up with them or dismiss the pain) Inconvenience (too busy to see doctor) Fear Embarrassment (particularly for young men and women) Presentation - Mass (pressure, pain, often palpable, causes obstruction or ulceration/perforation) - Metastasis (invasion of circulation, organomegaly, effusions) -- could be that patient has no symptoms of the primary but presents with metastatic symptoms - Asymptomatic (on routine investigation/screening) - Non-metastatic manifestations of malignancy or "para-neoplastic syndromes" Paraneoplastic syndromes are symptoms that are not due to the local presence of cancer cells (ie. Tumor invading/pressing on something) but rather humoral factors (ie. Hormones or cytokines secreted by the cancer) or immune factors (the immune response against the tumor) which include things like Cushing's, ADH secretion, electrolyte disturbance, Lambert-Eaton syndrome, Trousseau sign, anemia etc.

Poor prognostic factors for CUP

Poorly differentiated carcinoma, squamous cell carcinoma, neuro-endocrine carcinoma -- all spread rapidly Lymph node involvement, especially SCF (stem cell factor, a type of growth factor and cytokine) Many metastatic sites Males do worse Body habitus (overweight do worse, but also patients who lose >10% of weight do worse) Serum markers (ALP, LDH, CEA)

Risk of malignancy index

RMI = Ca125 levels x USS score x menopausal status RMI>200 needs a referral to a gynae-oncologist

Risk factors for germ cell tumors

Risk factors include family history (2% report a first degree relative, 10x increased risk), testicular maldescent (particularly if this is not fixed early on in life, it increases the temperature of the testes which is damaging to cells -- so orchidoplexy after the age of 2 (or none at all) is a risk factor), Klinefelter's syndrome and Down's syndrome.

Complications of testicular cancer

SVC obstruction Pleural effusion (due to lung metastases) PE Ureteric obstruction Therapy complications Pulmonary fibrosis (bleomycin) Cardiovascular risk Fertility problems Cardiovascular risk Tumor lysis syndrome (very common) High rates of long term survival mean that the long-term effects of chemotherapy and radiotherapy are significant. About 50% of men will have a low sperm count and fertility issues, therefore all men who require chemotherapy or radiotherapy should be offered sperm storage. If the sperm count is normal prior to chemotherapy, it will be normal after chemotherapy in 2/3 of men. Hypertension can happen following nephrotoxic chemotherapy. Survivors should be advised not to smoke due to an increased risk of cardiovascular disease. Smoking can also increase the risk of secondary malignancies (ie. Hematological malignancy and solid organ malignancies near the area where radiotherapy was given). Men also struggle with psychosexual issues due to sexual dysfunction and problems with body image.

Steps to managing CUP

Search for primary site Rule out potentially treatable or curable causes Characterize the clinico-pathological entity and treat the patient (decide if curative or palliative) Patients with nodal metastases of a poorly differentiated carcinoma or females with 'peritoneal cancers of a serious histological type' (behave like ovarian cancer) must not be missed. 80% of these can achieve remission.

Hormone secretion in lung cancer

Small-cell lung cancers produce ADH and ACTH Squamous cell cancers produce PTH and TSH

Signs of pleural effusion (common presentation of lung cancer)

Tachypnea Reduced chest expansion Deviated mediastinum Absent or diminished tactile vocal fremitus Dull percussion Absent or reduced breath sounds Reduced air entry Bronchial breathing above the level of the effusion (known as aegophony) Whispering pectoriloquy (increased vocal resonance) Pleural rub above the fluid

Investigations for CUP

The immunohistochemistry can help in some cases to rule out: neuro-endocrine tumors, lymphomas, germ cell tumors, melanomas, sarcomas and embryonal malignancies (especially in childhood). These are often very treatable and we can exclude them with immunohistochemistry. Most patients are over-investigated, so you need to ask whether the investigation will impact the management or outcome of the patient. If it does not affect the outcome, there is no reason to do the investigation. Possible investigations include: 1) Physical examination including head and neck, rectal, pelvic and breast 2) Blood tests (FBC, serum biochemistry, LFTs, urinalysis, fecal occult blood test) 3) Imaging (CT thorax, abdomen and pelvis) 4) Other (endoscopy if suspected GI primary, tumor markers) - Tumor markers are sensitive but not specific, they are rarely diagnostic - Examples include alpha-fetoprotein (AFP), beta human chorionic gonadotrophin (beta-HCG) and prostate-specific antigen (PSA) - If a female patient is there, you should be doing a breast examination and mammogram (even if examination is unremarkable) - PET-CT can contribute to management of tumors, especially in those with cervical lymphadenopathy and single metastases -- the PET CT excludes other metastases (it tells you where the cancer has spread)

Ovarian cancer overview

The incidence is 6900 cases per year. The peak age is 50-70 (median 63) and the mortality rate is high, with a 5 year survival of 50%. It is primarily a disease of postmenopausal women. The highest rates are seen in developed countries and in European-born Jews (most likely due to BRCA1 and BRCA2 inheritance).

Risk factors for lung cancer

The main risk factor is smoking. Other risk factors include radiation, air pollution, asbestos and existing conditions such as lung fibrosis. Squamous cell carcinomas are much more associated with smoking whereas adenocarcinomas are more associated with non-smokers.

Germ cell tumors overview

The most common type of testicular cancer is a germ cell tumors. There are two types of germ cell tumors: seminomas and non-seminomatous germ cell tumors (NSGCT). Both occur at the same rate, but seminomas tend to grow and spread more slowly than NSGCT. NSGCT can be divided into four categories: embryonal, yolk sac carcinoma, choriocarcinoma and teratoma. Seminomas are either classic (95%) or spermatocytic. On histology, seminomas will have sheets and cords of uniform cells while NSGCTs can have variety of appearances. Testicular germ cell tumors are relatively rare (8.1 per 100,000) with peak incidence at 25-35 and 55-65. It is one of the few curable cancers even if there is metastasis, the 5 year survival is 95.8%. Germ cell cancers multiply more rapidly than most other cancers and are therefore more susceptible to chemotherapy.

Types of breast cancer

There are multiple types of breast cancer. Invasive ductal carcinoma (most common, 70%) Invasive lobular carcinoma (second most common) Ductal carcinoma in situ (has a high risk of becoming invasive) Lobular carcinoma in situ (risk factor for cancer in either breast -- 7% at 10 years) Paget's disease of the breast presents with erythematous keratotic patches over the areola areas. It tends to be pre-malignant (in 50% of cases).

Symptoms of germ cell tumors

There is often a delay in the presentation but patients usually present with a testicular enlargement, decrease in size or swelling (painless, solid, unilateral mass), sometimes scrotal pain (20%) described as a 'dragging' sensation and less commonly a hydrocele, gynecomastia or a non-specific backache (10%).

Management of breast cancer

Treatment is through surgery, radiotherapy, hormone therapy, chemotherapy and biological therapy.

Tumor lysis syndrome

Tumor lysis syndrome is a condition that happens due to the death of a large number of cancer cells in a short period of time and presents with hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia (due to the sudden release of hormones from the cells). It can lead to cardiac arrest, arrhythmias, acute renal failure and DIC. It tends to happen in people with large tumors (high LDH increases risk), renal impairment and young age (<25) and can be precipitated by chemotherapy, radiotherapy, steroids, immune modifiers or surgery. It is managed with adequate hydration, electrolyte control (low K+ diet -- watch out for potassium, it will go up, no bananas or chocolate), aluminum hydroxide, hemodialysis, allopurinol (needs to be reduced with renal impairment, is nephrotoxic) and urate oxidase.

Classifications of CUP

Well-moderately differentiated adenocarcinoma (50%) Poorly or undifferentiated adenocarcinoma (30%) Squamous cell carcinoma (15%) Undifferentiated carcinoma (5%) Carcinomas with neuro-endocrine differentiation (rare)

Non-hormonal symptoms of lung cancer infiltration

Hoarse voice due to recurrent laryngeal nerve Paralyzed diaphragm due to phrenic nerve palsy (can see the diaphragm higher than normal on an x-ray) Superior vena cava obstruction (most commonly in SCL) Distension of veins in the neck/face (visible veins on head), redness and swelling of face, SOB, head fullness, chest pain, edema around eyes, headache worse in mornings, visual disturbance dyspnea, facial swelling, head fullness, cough, arm swelling, chest pain Symptoms can be aggravated by bending forward, stooping or lying down CXR findings include superior mediastinal widening (64%), pleural effusion (26%), right hilar mass (12%), bilateral diffuse infiltrates (7%), cardiomegaly (6%) Horner's syndrome due to damage to the sympathetic chain on one side (miosis, anhidrosis, partial ptosis and enophthalmos -- displacement of eyeball) Rib erosion (ribs are disintegrated leading to pathological fractures) Pericarditis Pleural effusion Adenocarcinoma and large cell (15%) lead to gynecomastia Small-cell cancers lead to Lambert-Eaton syndrome (encephalitis, leads to muscle weakness -- differentiate from Myasthenia gravis, difficulty walking and muscle tenderness) Lambert-Eaton myasthenic syndrome is a disorder of the neuromuscular junction and about 60% of patients with this have an underlying cancer, of which 60-70% are SCLC (followed by breast, thymus, GI) Causes proximal muscle weakness; myasthenia gravis affects the bulbar muscles while LEMS does not, but 30% of patients with LEMS will have dysphagia Adenocarcinoma can cause HPOA (wrist pain)

Hypercalcemia in lung cancer

Hypercalcemia is a medical emergency and occurs due to secretion of parathyroid hormone (PTH-rP), which 100x more potent than normal PTH; 10% of patients with lung cancer will manifest hypercalcemia at some point It is usually made by squamous cell cancers (NSCLC, head and neck, renal, SCC of esophagus, cervical etc.) It presents with rapid onset nausea, polyuria, polydipsia, dehydration, cardiac arrhythmia -- consider in anyone with cancer who has unexplained nausea Diagnosed as serum calcium >2.7 The life-saving intervention is saline hydration and IV bisphosphonate (saline is the FIRST STEP)

Hypocalcemia in cancer

Hypocalcemia is more common in patients with bone metastasis (breast, prostate, lung cancers) and it rarely occurs in tumors that secrete calcitonin (ie. Thyroid) therefore calcitonin can be used to screen or monitor medullary carcinoma of the thyroid The features of hypocalcemia are rare (tetany, neuromuscular irritability)

Breast cancer screening

In the UK, all women are offered breast cancer screening with mammography every 3 years between the ages of 50 and 70 years. After the age of 70 years women may still have mammograms but are 'encouraged to make their own appointments'. Women at higher risk can have screening at a younger age.

SIADH in cancer

Inappropriate ADH secretion (SIADH), usually in small cell lung cancers (10% of SCLC patients develop it, also happens in pancreatic, prostate) and is the most common endocrine paraneoplastic syndrome Some drugs can also cause this (ie. Cisplatin) but it is more common as a paraneoplastic syndrome It is often asymptomatic but can lead to CNS toxicity (fatigue, headaches, confusion, seizures) Need to exclude non-malignant causes first (ie. CNS disease, infections, asthma, drugs) Diagnostic criteria: Hyponatremia <130 Normal albumin and glucose Serum hypo-osmolality <275 Urine osmolarity > serum osmolality Urinary sodium >25 ADH not suppressed on suppression test Treatment is fluid restriction (0.5-1L/day) and democlocycline