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‘When is a stroke not a stroke?’ Danielle Hann Lucinda Lacey Anthony Li Emma Briggs Samu Pekwa History 79 year old Female Referred by GP 3/52 ago to A&E with ?cord compression P/C Right arm pain Right sided weakness History HPC 4/52 right arm pain 3/52 right leg weakness gradual onset Finding mobility increasingly difficult Presented to another A&E 2/52 prior with weakness but sent home Weakness progressively worsened Dizziness for 5 years but worse in last 3/52 History HPC contd. 40 year Hx of cervical spondylosis Negative signs Haemoptysis Paraesthesia Bladder/bowel dysfunction Sensory level No falls No visual problems • double vision, blurred vision History PMH TB with lymph node excision as child Rheumatic fever as child 40 year Hx cervical spondylosis DH & Allergies Nil NKDA History SH Lives with Husband (Well) Maisonette - bed and bathroom on top floor Previously fully independent in ADLs Husband does cooking and cleaning 2/52 prior to admission started using 1 stick for walking and chair transfers Ex smoker stopped 8 years ago 45 pack year Hx Alcohol Nil Examination On admission - from notes General Well Afebrile No weight loss Resp Sats - 96% on air No clubbing/cyanosis Trachea central Bilat air entry No creps/wheeze FEV1 36% predicted FVC 56% predicted PEF 22% predicted CVS P 80 reg BP - 170/66 HS I + II + 0 JVP No murmur/No carotid bruit Abdo Soft & non-tender No organomegaly Bowel sounds present Examination Neuro Left upper and lower limbs all 5/5 Wasting of small muscles of right hand Tested RUL Power Tested RLL Power Shoulder abduction Elbow flexion Elbow extension Finger flexion Wrist flexion 0/5 Hip flexion 3/5 3/5 0/5 3/5 3/5 Wrist extension 0/5 Hip extension Knee extension Knee flexion Ankle dorsiflexion Ankle plantarflexion 3/5 3/5 3/5 4/5 4/5 Examination Neuro contd Reflex Brachial Supinator Triceps Knee Ankle Plantars Right +++ ++ +++ +++ ++ Left ++ ++ ++ ++ ++ Tone and sensation normal No clonus Examination Neuro contd No hoarseness of voice CN II - XII No ptosis/Normal pupillary reactions Hoffmans -ve bilaterally No deep finger flexor reflex No pectoral reflex Neck No tenderness or pain on movement Impression and Plan Impression Left hemisphere CVA Wasting/no extensor plantars ?UMN Spinal cord compression No bladder or bowel dysfunction or sensory level Plan Bloods - FBC; U&E; Glucose; LFTs; CRP; Cholesterol C-spine and Chest x-ray (AP and Lateral) Results Bloods Hb WCC Plt MCV ESR CRP 14.8 8.6 275 85 21 3.0 Na K Cl Bicarb Urea Creat 135 4.2 96 29 4.7 75 Glucose Bilirub ALT ALP Alb Ca 5.8 10 8 66 37 2.32 Chol TG HDL LDL 7.1 0.68 2.0 4.8 Results contd CXR Features consistent with old TB in RUZ Lesion in RMZ peripheral, well demarcated, 2cm nodule No rib involvement No hypertrophic pulmonary osteoarthropathy Revised Plan CXR results and neurological signs indicate CT Head CT Chest CT guided biopsy (peripheral lesion) CT brain Results CT head Ring enhancing cystic mass in left petrous region consistent with cystic tumour or abscess (?old TB) CT chest probable lung primary right hilar lymph node Biopsy histology Poorly differentiated squamous cell carcinoma (Non-small cell carcinoma) Drug Treatment Ramipril Dexamethasone Simvastatin Ranitadine Lanzoprazole Management plan Neurosurgical opinion ?burr hole or craniostomy to drain cyst ?Radiotherapy Adjuvant brain Palliative lung No chemotherapy Home with large care package ASAP Lung Cancer Background Leading cause of cancer-related mortality in both men and women. Diagnosis at an advanced stage. Smoking-related damage to the heart and lungs, making aggressive surgical or multimodality therapies less viable options. Epidemiology Men >Women (37.5 vs. 10.8 new cases/million) Most common malignancy-related deaths in men and women. 17.8% of cancer-related deaths Aetiology Smoking: Cigarette smoke contains N-nitrosamines and aromatic polycyclic hydrocarbons. hydroxylated by the P-450, leading to formation of carcinogens that cause formation of DNA adducts. 78% in men and 90% in women. risk is 13.3 times that of a person who has never smoked. varies with the number of cigarettes smoked. After quitting, risk increases for the first 2 years and then gradually decreases, but never returns to the same level. Aetiology Passive smoking: 15% of the lung cancers in nonsmokers are believed to be caused by secondhand smoke. Asbestos: x5 risk. Synergistic. Radon Others: Aromatic polycyclic hydrocarbons, beryllium, nickel, copper, chromium, cadmium, and diesel exhaust. Classification Upper tract: Tracheal Laryngeal Lower tract: Bronchial- most common primary (90-95%) Carcinoid Metastatic Pleural tumours. Classification Bronchogenic Small (Oat) Cell ~20% Adenocarcinoma 35-40% Non-Small Cell ~80% Squamous 25-30% •SCLC exhibits aggressive behaviour: •rapid growth, •early spread to distant sites, •exquisite sensitivity to chemotherapy and radiation •frequent association with distinct paraneoplastic syndromes. •Surgery usually plays no role in its management Large-cell 10-15% Pathophysiology Amplification of oncogenes and inactivation of tumor suppressor genes in NSCLC. Mutations involving the ras family of oncogenes. 3 members: H-ras, K-ras, and N-ras. Encode a protein on the inner surface of the cell with GTPase activity and may be involved in signal transduction. Almost exclusive to adeno Ca (30% 0f cases). Natural History Cytological Atypia Piling of bronchial mucosa Irregular, warty, erosive lesion Fungates Intra-luminal mass Rapid penetration, infiltration of peribronchial tissue. •Tissue: •greyish white •haemorrhagic •Necrosis-cavitating Intraparenchymal mass (caulifower) •Spread: •Lymphatic •Haematogenous Histology Adenocarcinomas: form glands and produce mucin. Identified with mucicarmine or periodic acidSchiff (PAS) staining. WHO classification of adeno Ca: (1) (2) (3) (4) acinar papillary bronchoalveolar mucus secreting Histology Squamous cell carcinoma: distinct dose-response relationship to tobacco smoking usually develops in proximal airways, classically presents as a cavitary lesion Type most often associated with hypercalcemia. Progresses through stages of squamous metaplasia to carcinoma in situ. Well-differentiated squamous cell carcinomas contain keratin pearls. Histology Squamous Cell: Microscopic examination reveals cells with large irregular nuclei and coarse nuclear chromatin with large nucleoli. Cells are arranged in sheets and intercellular bridging is diagnostic. Histology Large Cell: Typically presents as a large peripheral mass on CXR. Histologically, sheets of highly atypical cells with focal necrosis, with No evidence of keratinization or gland formation Patients with large cell carcinoma are more likely to develop gynecomastia and galactorrhea Prognosis Estimated 5-year survival rates: Stage IA - 75% Stage IB - 55% Stage IIA - 50% Stage IIB - 40% Stage IIIA - 10-35% Stage IIIB - <5% Stage IV - <5% In Europe, the 5-year overall survival is 8% Prognostic Factors Tumour related: Physical Stage/Grade Biochemical Molecular Haematological Host related: Age Sex Performance Status Weight loss Presentation Local effects of tumour in bronchus Spread to mediastinum Spread to pleura and chest wall Spread to lymph nodes Distant blood bourne metastases Paraneoplastic (non-metatastic)complications Local effects of tumour in bronchus 1, Cough. 2, Haemoptysis. 3, Bronchial narrowing 4, Distal collapse 5, Finger clubbing Spread to mediastinum 1, Left recurrent laryngeal nerve paralysis 2, SVC obstruction 3, Compression of oesophagus 4, Phrenic nerve paralysis 5, Pericardial invasion Spread to pleura and chest wall 1, Pleural effusion 2, Chest wall pain 3, Pancoast tumours Pain in T1 dermatome Wasting in small muscles of hand Horner’s syndrome Spread to lymph nodes 1, Hilar lymphadenopathy – bronchial narrowing, retrograde obstruction of pulmonary lymphatics (lymphangitis carcinomatosis) 2, Mediastinal lymphadenopathy – can compress and invade other mediastinal structures. Distant blood-borne metastases Bone, liver, brain, adrenal glands, skin. Paraneoplastic complications 1, Pulmonary hypertrophic osteoarthropathy 2, Endocrine syndromes – Cushings, hypercalcaemia, gynaecomastia. 3, Neuromuscular syndromes - Peripheral neuropathy, cerebellar dysfunction, dermatomyositis. Investigations Imaging Laboratory studies Procedures Imaging Chest X-ray Hilar lymphadenopathy, area of pulmonary collapse, unresolved pneumonia, pleural effusion, lung abscess, peripheral mass, lymphangitis carcinomatosis, eroded ribs. Squamous cell carcinoma may be radiologically occult. It is slow growing and usually presents as a central mass that may cavitate. CT + MRI Chest and upper abdomen Brain Bone scintigraphy Laboratory studies Sputum cytological studies False-positive rate for sputum cytology is 1% False-negative rate is as high as 40%. Full blood count, LFTs Electrolytes Procedures 1, Bronchoscopy Establishes diagnosis and position of the tumour in the bronchial tree in over 70% 2, Mediastinoscopy 3, Thoracoscopy 4, CT-guided biopsy 5, Biopsy of other sites eg, enlarged palpable lymph nodes, liver, pleural and pericardial effusions. Staging Primary tumour (T) TX Malignant cells in bronchial secretions, no other evidence of tumour Tis Carcinoma in situ T0 None evident T1 <3cm, in lobar or more distal airway T2 >3cm / 2cm distal to carina / any size if pleural involvement or obstructive pneumonitis extending to hilum, but not all the lung T3 Involves the chest wall, disphragm, mediastinal pleura, pericardium / 2cm from, but not at carina T4 Involves the mediastinum, heart, great vessels, trachea, oesophagus, vertebral body, carina / malignant effusion is present Staging Regional Nodes (N) Distant metastasis (M) N0 None involved (after mediastinoscopy) N1 Peribronchial and/or ipsilateral hilum N2 Ipsilateral medistinum or subcarinal N3 Contralateral mediastinum or hilum, scalene or supraclavicular M0 None M1 Present Staging Stage Tumour Lymph Nodes Metastasis Occult TX N0 M0 I Tis, T1 or T2 N0 M0 II T1 or T2 N1 M0 IIIa T3 N0 or N1 M0 T1-T3 N2 M0 T1-T3 N3 M0 T4 N0-N3 M0 T1-T4 N0-N3 M1 IIIb IV TREATMENT Depends upon a variety of factors such as: Histopathologic type Tumour stage and characteristics Individual’s general health Medical problems that may affect treatment Non-Small cell Lung Carcinoma Surgical resection is best potentially curative therapy Only in those: Whose tumour is resectable With adequate respiratory reserve Without a major medical contraindication to surgery An agreeable patient N.B. For those who are not fit for surgery, Radiation and/or Chemotherapy are considered. Unresectable stage 3 treated with combined radio- and chemotherapy. Limited Small Cell Lung Cancer Highly chemosensitive Combination chemotherapy and Thoracic irradiation +/- prophylactic cranial irradiation is standard therapy for patients with limited SCLC. Radiotherapy reduces local recurrence by 50%, but still with isolated local failure rates between 25% to 30% Surgery may improve control at the local site. Limited Small Cell Lung Cancer 5 - 10% of SCLC cases are found in combination with other lung cancer histologies including adenocarcinoma or squamous cell carcinoma. Surgery may be necessary to treat the nonsmall cell component. Late recurrences may be of non-small cell type (a new primary) and may be treated surgically if standard criteria for operability are met. Extensive Small Cell Lung Cancer Chemotherapy: - Rarely curative - Significantly improve survival - Palliative - The optimal induction are either Etoposide with Cisplatin or Cytoxan, Doxorubicin and vincristine. Surgery has little role to play in stage 3 tumours as it does not significantly contribute to longterm survival. Lung Cancer in the Elderly 80% are of NSCLC Less aggressive treatment Quality of life is equally important Radiation therapy is valuable for both types Monochemotherapy is more approppriate in those over 75. Unresectable NSCLC stage 3 best treated with combined chemo- and radiotherapy Lung Cancer in the Elderly Limited stage SCLC treated combination chemotherapy and radiotherapy Recent minimally invasive techniques more suitable Age alone is not a factor in determining the best operative procedure for lung cancer Good health is essential to tolerate treatment Palliative care Multidisciplinary approach Psychological support Symptom control essential (Pain, Nausea, Vomiting, Anorexia, Malaise,Weakness, Bowel obstruction, Respiratory symptoms, etc.)