Lung cancer occurs in patients with COPD and IPF. Unclear if trans- plantation itself increases the risk of lung cancer. May progress unusually rapidly, mimick ing infection. Differential diagnosis of CXR nodules following lung transplant - Post-transplant lymphopro liferative disease - Infection (Pseudomonas, Nocardia, aspergilloma, TB) - Disease recurren ce - Primary lung cancer. Further information Boehler, E. Post-transplant bronchiolitis obliterans. Eur Resp J 2003; 22: 1007 \200\22318 This page intentionally left blank 331 Chapter 33 Mediastinal abnormalities Anatomy 332 Mediastinal abnormalities 1 334 Mediastinal abnormalities 2 336 CHAPTER 33 Mediastinal abnormalities 332 The mediastinum is the area within the center of the chest containing the heart, great vess els, nerves, lymph nodes, trachea, esophagus, and thymus. Two-thirds of mediastinal masses are benign. Age 20 \200\22340, presence of symp- toms and anterior location of a mass are a ll associated with an increased likelihood of malignancy. Common symptoms of mediastinal di sease include cough, chest pain, and dyspnoea, as well as symptoms relating to any struc- t ure being compressed, such as dysphagia, stridor, or SVCO. Mediastinal disorders can also b e asymptomatic. They may be found incidentally fol- lowing a CXR. Anatomy Anterior mediastinum The area behind the body of the sternum and in front of the \201 bro us pericardium. Contains the thymus, which also extends superiorly. Posterior mediastinum The area in front of the vertebral bodies and behind the \201 brous pericardium. Contains the spinal nerve roots, the descending aorta and esophagus, the azyg os and hemiazygos veins, the thoracic duct, and vagus and splanchnic nerves. Superior mediastinum The area located between the thoracic inlet superi- orly, the manubriu m of the sternum anteriorly, by the superior 4 thoracic vertebrae posteriorly and inferiorl y where a horizontal plane would cross through the sternal angle. It contains the aortic ar ch and its large branches and the upper half of SVC. It also contains the trachea, the esop hagus, the thoracic duct, and the phrenic, vagus, cardiac, and left recurrent laryn- geal n erves. Middle mediastinum The area containing the heart and pericardium, the ascending aorta, the lower half of the SVC, part of the azygos vein, the pulmonary arteries and veins, the trach eal bifurcation, phrenic nerves, and the IVC. These areas are easily seen on a lateral CXR. Oesophageal cyst Retrosternal thyroid Great vessels Thymus Lymph nodes o ste rio r Teratoma/ dermoid cyst Anterior Neurofibroma Middle P Pleuro- pericardial cyst Heart Hiatus hernia Fat pad Fig. 33.1. Anterior, posterior, superior, and middle mediastinum ANATOMY 333 Likely nature of mediastinal mass according to anatomical site Anterior mediastinal mass - Thymoma (superior) - Thyroid (superior) - Germ-cell tumor - Lym phoma - Ascending aortic aneurysm - Pleuropericardial cyst - Pericardial fat pad - Morgagni anterior diaphragmatic hernia (p 343) Superior mediastinal mass - Bronchogenic cyst Poster ior mediastinal mass - Neural tumor - Foregut duplication or cyst - Lipoma - Descending aor tic aneurysm - Bochdalek posterior diaphragmatic hernia (p 343). Approach to the patient with a mediastinal mass - Full history - Examination, including ski n, lymphadenopathy (neck, axillae, groins) and testes Look for fatiguability: ptosis, opthalmoplegia, inability to maintain upward gaze Look for signs of SVCO or stridor - Blood tests, including AFP, BHCG, anti-acetyl choline r eceptor anti- body CXR and lateral CXR (if not already done) - Arrange CT scan of chest - Try and locate old C XRs. CHAPTER 33 Mediastinal abnormalities 334 Mediastinal abnormalities 1 Neural tumors mostly occur in the posterior mediastinum. 75% ar e benign in adults. - Schwannomas and neuro \201 bromas are benign peripheral nerve sheath tumors. They may be multiple. Usually asymptomatic, although can cause segmental pain. Slow ly enlarge and, rarely, can cause cord compression, with dumb-bell shaped tumors straddling the intervertebral foramen. Can be surgically excised Malignant peripheral nerve sheath tumors or neurosarcomas include new malignant growths and benign neuro \201 bromas that have undergone malignant change. They may cause systemic fe atures of malignancy and can invade locally and metastasize Autonomic nervous system tumors including neuroblastomas and ganglioneuromas, range from benign to malignant. Surgical removal is the treatment of choic e, with radiotherapy and chemotherapy if the tumor is malignant. Thymoma Tumor of epithelial origin arising in the thymus. May contain functioning thymic ti ssue. M = F. Rare below age 20. Myasthenia gravis is present in 30 \200\22340% of patients with a thymoma; this is often unimproved after thymectomy and may even develop after the th ymoma is removed. 20% of patients presenting with myasthenia gravis are found to have a thy moma, particularly if patients are over 50 and male. This group is likely to have positive acetylcholine receptor (AChR) autoantibodies, which bind to AChRs at the postsynaptic motor endplate, decreasing available acetylcholine binding sites, causing nerve fatigability. Patients with thymomas are usually symptomatic with pain, dyspnoea, dysphagia, or myastheni a gravis symptoms. Thymomas contained within the thymic capsule tend to be benign, although they do have malignant potential; those that have extended outside the capsule are maligna nt, and may involve local structures or metastasize. Diagnose with CT and treat with surgic al excision of the thymus, avoiding prior FNA or biopsy as this may cause tumor seeding out side the capsule. Consider post-operative radiotherapy and chemotherapy for invasive tumors , especially those not completely excised. Thymectomy is indicated in patients with myasthe nia gravis even without thymoma, as it may lead to symptomatic improvement. This gives best results in those with detectable AChR antibody levels and younger patients early in the di sease course, particularly those with severe disease. Thymic cyst may be congenital or acqu ired secondary to in \202 ammation. Asymptomatic unless large and causing symptoms of comp ression. Benign, but usually treated with surgical excision, as diagnostic certainty may be dif \201 cult. Thymic carcinoid Not associated with myasthenia gravis and behaves aggress ively, with local recurrence and metastasis. May be associated with Cushing \200\231s syndr ome. Treatment with surgery, chemotherapy, or octreotide. Also: thymic carcinoma, thymic lipoma, and thymic hyperplasia. MEDIASTINAL ABNORMALITIES 1 335 Germ cell tumors Arise from immature germ cells, which fail to migrate during development. Tend to be in an anterior and mid-line location. - Mature cystic teratomas represent 80% of germ cell tumors. These are benign and occur in young adults. M = F. Often asymptomatic, b ut can erode surrounding structures and cause symptoms. CXR shows well-de \201 ned mass, w hich may contain \202 ecks of calci \201 cation. Treatment is by surgical excision Seminoma occurs in men age 20 \200\22340 years. Mediastinal seminomas are malignant and almost always arise within the thymus and are histologically indistinguishabl e from those occurring in the testes. Can be primary mediastinal tumor or metastasis from t esticular tumor; therefore always examine testes. Patients frequently present with chest pa in. CXR shows non-calci \201 ed lobulated anterior mediastinal mass, con \201 rmed with C T. Serum AFP is normal and this aids diagnosis. Diagnose with surgical biopsy. Surgical exc ision is not recommended as is usually incomplete. Treatment is with cisplatin- based chemo therapy initially, which can cause infertility and therefore patients may wish to consider sperm banking before treatment. Tumors are radiosensitive, so radiotherapy used if they are bulky. Long-term survival expected in 80%. Better prognosis than non-seminomatous germ cel l tumors Non-seminomatous germ cell tumors (including choriocarcinoma, teratocarcinoma, and yolk sac tumors) are all malignant and occur in men in their 30s. They are symptomatic due to local invasion and they metastasize. CXR shows mediastinal mass and diagnosis is with surgical biopsy. BHCG and AFP are raised. Treatment is with cisplatin-ba sed chemotherapy. BHCG and AFP are markers of disease and fall with tumor response. Thyroid Retrosternal goiter occurs, especially in older women. Usually asymptomatic unless large and compressing the trachea, causing dyspnoea and stridor. May be seen on plain CXR. CT and radioactive iodine isotope scans are helpful in diagnosis. Flow \200\223volume loops are abnormal if there is tracheal compression. Surgery is recommended if there is airway c ompro- mise, but can lead to tracheomalacia afterwards. Also: parathyroid adenoma CHAPTER 33 Mediastinal abnormalities 336 Mediastinal abnormalities 2 Lymphoma The mediastinum is frequently involved in patients wit h Hodgkin \200\231s lymphoma. CT scan is necessary to assess the extent of this and to asse ss response to treatment. To establish the histological diagnosis of lymphoma, an adequate tissue sample is required; this should be from a biopsy, rather than a \201 ne-needle asp irate. This may be best achieved surgi- cally, via mediastinoscopy. Examine patient for per ipheral lymph nodes, as these may be easier to biopsy. Treatment is with chemotherapy initi ally. Enlarged lymph nodes - Metastases from breast, lung, and oesophageal cancer - Castleman \200\231s disease Giant lymph node hyperplasia. Rare. Two forms: \200 Angio-follicular hy perplasia causing mediastinal or hilar lymph node mass. Often asymptomatic or may cause cou gh or wheeze due to localized compression. Non-progressive. May have fever and raised ESR. Nodal biopsy shows follicles of pericapillary lymphocytes and proliferation of the plump an d eosinophilic capillary endothelial cells. Removal of nodes may improve symptoms. Can also occur on pleura Multicentric Castleman \200\231s disease is a more aggressive disease that may occur in ass ociation with HIV infection. Lymphoproliferative disorder with prominent systemic symptoms, as well as generalized lymph node enlargement, hepatosplenomegaly, paraproteinaemia, and s kin rash. Biopsy shows prominent plasma cell in \201 ltration. Related to IL-6 over-produc tion and human herpes virus-8 infection. Treatment is with steroids chemotherapy (doxoru bicin, vincris- tine, and cyclophosphamide), but prognosis is poor. Can progress to non-Hod gkin \200\231s lymphoma. Rapidly fatal without treatment Also: lymphangioma Cysts - Foregut duplications or bronchogenic cysts can be related to the esophagus or the airways, especially near the carina. Lined by respira- tory epithelium. Of ten diagnosed in childhood, as they cause dyspnoea, stridor, or cough due to limited space to expand. Seen on CXR and CT and treated with surgical excision Pleuropericardial cysts mostly occur at the cardiophrenic angles and can measure up to 25 c m diameter. M = F. Usually asymptomatic, but may cause chest pain. CXR shows smooth round s hadow abutting the heart. Excision can be carried out at thoracoscopy, but conservative man agement is favored. Also known as springwater cysts. MEDIASTINAL ABNORMALITIES 2 337 In \202 ammation - Mediastinitis occurs after oesophageal perforation or rupture, due to malignancy, instrumentation, or vomiting (Boerhaave \200\231s syndrome). Patients are il l, with pain and fever. CXR may show widened medi- astinum or air in the mediastinum. Pneum othorax or pleural effusion may also be seen. Treatment includes repairing the defect, pare nteral feeding, and antibiotics. High morbidity and mortality Mediastinal \201 brosis Rare idiopathic condition that occurs in middle age. Symptoms dep end on which aspects of the mediastinum are involved, but may include dyspnoea, wheeze, hae moptysis, hoarse voice, dysphagia, pulmonary hypertension, SVCO. CXR shows a widened medias tinum. Diagnosis made on biopsy, particularly to exclude malignancy. Treatment is supportiv e; steroids and surgical debulking ineffective. Prognosis variable, depending on sites invo lved. May be associated with retroperitoneal \201 brosis, radiotherapy, methy- sergide, a uto-immune disease, or infection with TB, histoplasmosis, Aspergillus, or Nocardia. Mediastinal emphysema or pneumomediastinum. Can be caused by sneezing, straining, Valsalva maneuvers, vomiting, substance abuse, par- turition, positive pressure ventilation, instrum entation, or trans-bronchial biopsy. Usually symptomless, but occasional pain. Hamman \200 \231s sign may be present (click with each heart beat on auscultation over lung). Treat wit h high- \202 ow oxygen. Resolves spontaneously. Vascular Aortic aneurysms are usually asym ptomatic, but symptoms relate to compression of adjacent structures. May diagnose on CXR as a widened mediastinum. This is best imaged via CT or MRI. Surgery should be considered to prevent death from rupture. Further information Duwe BV et al. Tumors of the mediastinum. Chest 2005; 128: 2893 \200 \223909 This page intentionally left blank 339 Chapter 34 Pediatric lung disorders pertinent to adult patients Chronic lung disease of prematurity 340 Viral wheeze and asthma 342 Congenital abnormalitie s 343 CHAPTER 34 Pediatric lung disorders 340 This chapter concentrates on pulmonary conditions that occur in child- hood and may become increasingly relevant to adult practice. Chronic lung disease of prematurity Chronic lung disease of prematurity (CLD), formerly kno wn as bronchopulmonary dysplasia (BPD). Advances in neonatal medicine have led to the impro ved survival of premature babies with immature lungs and respiratory disease. Babies born a t lower gestational ages are surviving into adulthood, due to therapy with antenatal steroi ds to prevent respira- tory distress syndrome and the use of arti \201 cial surfactant to decrease the surface tension of the neonatal alveolar membrane. There have also been improv ements in ventilatory techniques. CLD usually occurs in babies who have been mechanically v entilated. Usually caused by barotrauma from prolonged ventilation, high-pressure ventilation, and/or ventilation with high oxygen concentrations. Typical presentation is a premature baby who remains oxygen-dependent after 36 weeks post-c onceptional age. It is now infrequent in those born at 30+ weeks and weighing more than 120 0 g. Mortality of 25 \200\22330% with severe CLD. May require prolonged home oxygen therapy , up to 1 year or beyond. 50% of infants with CLD will need hospital re-admission during th eir \201 rst year with respiratory infection. Some may have signi \201 cant pulmo- nary sequelae during childhood and adolescence, with chronic hypoxia and pulmonary hypertension, but the majority of children with CLD do not have signi \201 cant ongoing respiratory sym ptoms. Children may have disabilities associated with prematurity, such as cerebral palsy o r learning dif \201 culties. Pathology Cytokine-mediated scarring and repair. Early in \202 ammatory phase: bronchial n ecrosis, alveolar destruction, capillary permeability, and associated obliterative bronchio litis. Subacute \201 broproliferative phase: type II pneumocyte hyperplasia, bronchial an d bronchial smooth muscle hyper- trophy, and interstitial and peri-alveolar \201 brosis. Chronic \201 bro-proliferative phase airway remodeling for up to 1 year. Prior to surfact ant use, these changes were more severe. PFTs Functional respiratory abnormalities persist with increased airway resistance and airw ay hyperresponsiveness. RV and RV/TLC are raised, indicative of air trapping. Air trapping improves over 3 \200\2234 years as lung growth occurs; however, small airway abnormalities persist, at least until the age of 10. Chest radiology Persisting mild to moderate abnormalities, with multi-focal areas of reduce d lung attenuation and perfusion, bronchial wall thickening, and decreased bronchus:pulmona ry artery diameter ratios on CT. These radi- ological abnormalities correlate with physiolo gical evidence of air trapping. Adulthood There are few longitudinal studies beyond childhood and it is unclear what the si gni \201 cance of CLD of prematurity is to adult lung disease. This page intentionally left blank CHAPTER 34 Pediatric lung disorders 342 Viral wheeze and asthma A controversial area. Wheezing is common in infants and toddlers, a nd is often due to viral respiratory tract infections, causing a viral-induced wheeze. This has been found to be associated with passive cigarette smoke exposure, contact with other children, and not being breast-fed. This transient early wheezing is distinct from childhoo d asthma. The children are not atopic and have no family history of such. The wheeze has re solved usually by the age of 3, although they may persist in having airway hyperactivity fo r many years. Children with asthma tend to have a family history of eczema with concomitant atopic dermatitis and develop their symptoms at any age, but usually slightly later (by th e age of 5). Half of them have mild symptoms, which regress by puberty. Those with more sev ere disease, requiring regular inhaled steroids, often have disease that persists into adul t life. Treatment for young children is based on persistent symptoms and atopy. Drugs which may be effective include inhaled corticosteroids and leukotriene receptor antagonists. CONGENITAL ABNORMALITIES 343 Congenital abnormalities Tracheomalacia Floppy trachea, usually associated with oesophageal atresia. Rarely will require intubation or tracheostomy. Congenital lobar emphysema Over-i n \202 ation of a lobe due to local- ized bronchomalacia or bronchial obstruction. May cau se wheeze or produce chest deformity. Often resolves spontaneously. Diaphragmatic hernia A diaphragmatic defect, causing bowel to be present in the chest. This may cause respiratory distress soon after birth and may have been detected during the antenatal period by USS, or it may be completely asymptomatic and found incidentally on CXR, with bowel seen in the ch est. There are two types. Bochdalek hernia is the congenital absence of posterolateral part of diaphragm, with associated hypoplastic lung due to bowel limiting growth. Treatment is with surgical repair of the diaphragmatic defect, but survival rate is only 50% due to unde r- lying lung problems. Morgagni hernia is anteromedial herniation through the foramen of M orgagni, which is more commonly found in adulthood. It may be asymptomatic or cause symptom s of fullness, tightness, or pain in the anterior chest; it does not cause intestinal obstr uction. CXR shows a cardiophrenic angle density. Surgical repair is dif \201 cult and is u sually not necessary. Cystic adenomatoid lung Excessive overgrowth of bronchioles with mult iple cysts occurring in a section of lung. Commonly affects left lower lobe. Can be diagnos ed antenatally. Can present in the same way as con- genital lobar emphysema. May be mistake n for diaphragmatic hernia. Treatment is by resection of the affected lobe, but there may b e space- occupying effects of the abnormal lobe that can cause morbidity and mor- tality, e .g. due to vena cava obstruction. Pulmonary sequestration/sequestrated segment Segment of l ung parenchyma with no bronchial connection that is unventilated. May be sup- plied by aber rant artery from the aorta and have anomalous pulmonary drainage to the right atrium. Can b e intralobar, sharing pleura with the rest of the lung, or extralobar, which is separated f rom the lung by a lining of pleural tissue. Mostly left-sided; 75% are situated between the diaphragm and left lower lobe. Associated with other congenital abnormalities in 60% of ca ses. Can be a chance \201 nding on CXR at any age, when cystic change may be seen in this area. Contrast CT or MRI may aid diagnosis. Surgical resection may be necessary if there i s repeated infection in this segment. MacLeod \200\231s syndrome Focal hyperlucency of lung or lobe, due to parenchymal and vascular maldevelopment, following a childhood bron- chiti s or bronchiolitis. Usually asymptomatic, and is diagnosed on CXR, which shows a hypertrans lucent lung with reduced vascular markings and a small pulmonary artery. This page intentionally left blank 345 Chapter 35 Pleural effusion Clinical features and imaging 346 Malignant pleural effusion: causes and investigations 348 Malignant pleural effusion: management 350 Parapneumonic effusion and empyema: de \201 ni tion and clinical features 352 Parapneumonic effusion and empyema: bacteriology and investigations 354 Parapneumonic effusion and empyema: management and outcome 356 Tuberculous pleural effusion 358 Other causes 360 CHAPTER 35 Pleural effusion 346 Clinical features and imaging A pleural effusion results from the accumulation of abnormal volumes (>10 \200\22320 ml) of \202 uid in the pleural space. Pleural effusions are commo n and are associated with many different diseases; see Chapter 8 for a step- by-step approa ch to the diagnosis of a patient with a pleural effusion, differential diagnosis of transud ates and exudates, and details of pleural \202 uid analysis. Clinical features - May be asymptomatic, or associated with breathlessness, dry cough, pleuritic chest pain (suggesting pleural in \202 ammation), chest \200\230heaviness \200 \231, and sometimes pain referred to the shoulder or abdomen Signs on examination include reduced chest expansion, reduced tactile vocal fremitus, a sto ny dull percussion note, quiet breath sounds, and sometimes a patch of bronchial breathing above the \202 uid level. A friction rub may be heard with pleural in \202 ammation. Imaging CXR - Sequential blunting of posterior, lateral, and then anterior costophrenic angles are seen on radiographs as effusions increase in size PA CXR will usually detect effusion volumes of 200 mL or more; lateral CXR is more sensitiv e and may detect as little as 50 mL pleural \202 uid - Classical CXR appearance is of bas al opacity obscuring hemidiaphragm, with concave upper border. Massive effusion may result in a \200\230white-out \200\231 of the hemithorax, with mediastinal displacement away from the effusion; lack of mediastinal shift in such cases raises the possibility of associated volume loss due to bronchial obstruction from a primary lung cancer Other CXR appearances include rounded or lentiform shadowing in loculated interlobar effusi ons, and diffuse shadowing throughout the hemithorax on supine \201 lms CXR appearance may suggest the underlying diagnosis, e.g. bilateral effusions with cardiome galy in cardiac failure; massive effusions are most commonly due to malignancy. Ultrasound is extremely sensitive at detecting \202 uid volumes of 100 mL or more, and is useful for distinguishing pleural \202 uid from pleural masses or thickening, and for de monstrating loculation. CT chest with pleural contrast is useful in distinguishing benign and malignant pleural dis ease: nodular, mediastinal, or circumferential pleural thickening are all highly speci \201 c for malignant disease. CT may also reveal evidence of extrapleural disease, e.g. lym phadenopathy or parenchymal change, which may suggest a diagnosis such as cancer or tubercu losis. Role of MRI is unclear; it may have increasing role in distinguishing benign from malignant pleural disease. CLINICAL FEATURES AND IMAGING 347 Pleural thickening - Pleural \201 brosis and thickening may follow previous episodes of p leural in \202 ammation. Causes include previous empyema, tuberculous pleuritis, rheumatoi d pleuritis, haemothorax, thoracotomy, and asbestos exposure (diffuse pleural thickening, p 111) - May be asymptomatic or cause breathlessness - CXR features include blunting of the costophrenic angle or apices, sometimes with associated calci \201 cation Ultrasound or CT may be required to distinguish from a pleural effusion Treatment is dif \201 cult and usually unnecessary; decortication may be considered. CHAPTER 35 Pleural effusion 348 Malignant pleural effusion: causes and investigations Epidemiology Commonest cause of exuda tive pleural effusion in patients older than 60 years. About 40 000 cases of malignant effu sion each year in the UK. Causes Most malignant effusions are metastatic, with lung and bre ast the most common primary sites (Table 35.1). Table 35.1 Primary sites and frequency Primary site Approximate frequency (%) Lung 37 Breast 16 Lymphoma 10 Mesothelioma 10 Genitourinary tract 9 Gastrointestinal tract 7 Unknown primary 10 Other, rarer tumors include sarcoma, melanoma, leukemia, and myeloma; almost any malignant tumor may spread to the pleural cavity. Mesothelioma is an important cause of malignant eff usions and is dis- cussed on p 114. Clinical features Breathlessness is the main symptom; c hest pain, cough, weight loss, and anorexia may also be present. A small proportion of pati ents are asymptomatic. Effusions may be unilateral or bilateral, and are frequently large v olume. Differential diagnosis Consider other potential causes of pleural effusion in patien ts known to have cancer, e.g. due to pneumonia, pulmonary embolism, radiotherapy, pericardi al disease, or drugs. Investigations A strategy for investigating the patient with an undia g- nosed pleural effusion is detailed on p 48. Key investigations in patients suspected to have a malignant effusion are: 1. Pleural \202 uid cytology Sensitivity for malignancy is about 60%; yield is increased by analysis of a second, but not a third sample. Immunostain ing of malignant cells may provide clues as to the likely primary site. Visualization of mo noclonal cells in \202 uid on \202 ow cytometry may support a diagnosis of lymphoma. 2. CT chest with pleural contrast Nodular, mediastinal, or circumferential pleural thickening on CT are highly speci \201 c for malignant disease. May also demonstrate extrapleural di sease, e.g. lymphadenopathy. MALIGNANT PLEURAL EFFUSION: CAUSES AND INVESTIGATIONS 349 3. Pleural biopsy histology Required in cytology-negative cases. Options: - CT-guided cutti ng needle biopsy has been demonstrated to be a more effective diagnostic test for malignant pleural disease than Abrams \200\231 pleural biopsy (sensitivity 87% in CT-guided biopsy g roup vs. 47% in Abrams \200\231 group) Ultrasound-guided needle biopsies are also effective and relatively straightforward to perform Thoracoscopy is an extremely useful investigation allowing direct visuali- zation of the pleural space with a high sensitivity (90%) for biopsies. Therapeutic talc po udrage (talc is \200\230puffed \200\231 directly on to the pleural surfaces) may be perfor med at same time, with a pleurodesis success rate >80%. Can be performed under general anes thesia, although well tolerated with sedation and local anesthesia. Complications (such as empyema) are rare. Serum tumor markers (CEA, CA19 \200\2239, CA15 \200\2233, CA125, PSA) may be helpful in the investigation of patients with malignant effusion of unknown primary, although their diagn ostic and prognostic value are limited. Prognosis Median survival 3 \200\22312 months from diagnosis; shortest in lung cancer, long est in mesothelioma and ovarian cancer. Pleural \202 uid pH <7.3 tends to be associated w ith shorter survival (median survival 2.1 months) and decreased success of pleurodesis. Further information Antunes G et al. BTS guidelines for the management of malignant pleural effusions. Thorax 2003; 58 (suppl. II): ii 29 \200\22338 Maskell NA et al. Standard pleural biopsy vs CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomized controlled trial. Lancet 2003; 361: 1326 \200\22331 CHAPTER 35 Pleural effusion 350 Malignant pleural effusion: management Key points in \202 uencing the management of malign ant effusions are: - Symptoms, performance status, and wishes of the patient - Sensitivity of the primary tumor to chemotherapy, e.g. small cell lung carcinoma, lymphoma, ovarian and breast carcinoma may respond to chemotherapy, although in some cases pleural effusions rem ain problematic and require additional treatment Extent of lung re-expansion following effusion drainage. Treatment options Observation and follow-up if asymptomatic. Therapeutic pleural aspiration of 1 \200\2231.5 L pleural \202 uid to improve breath- les sness. Can be performed at the bedside as a day-case procedure, avoiding hospital admission . Useful in the palliation of breathlessness in patients with a poor prognosis and in rare cases where effusion reaccu- mulates very slowly. Most effusions recur within 1 month of as piration, and these patients should be considered for pleurodesis; repeated aspiration may be inconvenient and uncomfortable for the patient, and carries a risk of complications such as empyema, pneumothorax, and tumor seeding (in mesothelioma). If the breathlessness does not improve following \202 uid aspiration, then there is littl e to be gained by repeated aspiration and other causes of breathlessness should be consider ed, e.g. lymphangitis carcinomatosa, pul- monary embolism. Intercostal chest drainage and pleurodesis The aim of pleurodesis is to seal the visceral p leura to the parietal pleura with adhesions to prevent pleural \202 uid accumulating. The success of pleurodesis depends on the degree of apposition of the visceral and parietal pl eura, which depends on the degree of lung re-expansion following drainage of the effusion. \200\230Trapped lung \200\231 occurs when tumor encases the visceral pleura and pre- vents lung expansion. Lung expansion may also be inhibited by a proximal airway obstruction or b y a persistent air leak (e.g. after tearing of a friable tumor-in \201 ltrated lung on re- expansion). Trapped lung may also be caused by non-malignant, \201 brotic processes, e.g. rheumatoid pleuritis, haemo- thorax, tuberculosis. The patient should be admitted and the effusion drained with an inter- costal tube. If lung fully re-expands on CXR, proceed to pleurodesis (see p 775). If lung fails to re-expand fu lly (trapped lung; CXR shows a pneu- mothorax or hydropneumothorax), consider chest drain s uction, which may encourage lung expansion and allow pleurodesis. MALIGNANT PLEURAL EFFUSION: MANAGEMENT 351 Treatment options for trapped lung or failed pleurodesis - Pleurodesis may be successful de spite only partial lung re-expansion and should still be considered. It may be repeated if unsuccessful initially Repeated therapeutic pleural aspiration - Intrapleural \201 brinolytics (e.g. streptokina se 250 000 IU) may be of bene \201 t in the management of multiloculated effusions resista nt to drainage and pleurodesis, encouraging free \202 uid drainage and in some cases enab ling successful pleurodesis. Hemorrhage is a theoretical complication, although it appears to be uncommon Thoracoscopy enables the disruption of pleural adhesions and may have a role in facilitating pleurodesis in select patients with trapped lung Long-term in-dwelling pleural catheter may be bene \201 cial in patients with trapped lung and frequent accumulation of symptomatic effusions, and avoids the need for recurrent pleu ral aspiration. The most frequent complications are tumor seeding around the drain site and pleural space infection. Can be inserted as a day-case procedure. Needs addi- tional out-p atient support (e.g. trained district nurse or respiratory specialist nurse), although most patients perform the drainage them- selves after education Pleuroperitoneal shunts are effective in patients with trapped lung or failed pleurodesis, in the absence of multiple loculations. Shunting of \202 uid may occur spontaneously, at high pressures, or may require manip- ulation of a percutaneous pump chamber, inserted at t horacoscopy or mini-thoracotomy. Main problem is shunt occlusion, which occurs in at least 10% of cases and necessitates shunt removal. Malignant spread may also occur Surgical parietal pleurectomy may be performed as VATS (video-assisted thoracoscopic surger y). The procedure is effective in the management of refractory malignant effusions. May be useful in a minority of patients with good performance status and prognosis. Not suitable f or patients with heavily diseased visceral pleura and trapped lung; consider in patients wh o have failed pleurodesis Palliative care team involvement should also be considered. CHAPTER 35 Pleural effusion 352 Parapneumonic effusion and empyema: de \201 nition and clinical features De \201 nition a nd pathophysiology Pleural effusions occur in up to 40% of patients with pneumonia. An init ial sterile exudate (simple parapneu- monic effusion) may in some cases progress to a compl icated parapneu- monic effusion and eventually empyema (Fig. 35.1). Exudative stage Simple parapneumonic effusion Clear sterile fluid with normal pH, glucose, LDH Frequently resolves with antibiotics alone Drainage not usually required Complicated parapneumonic effusion Fibrinopurulent stage Fibrin deposited and septations occur Fluid infected but not yet purulent; appears clear or cloudy/turbid pH< 7.2, glucose < 2.2 mmol/L and LDH > 1000IU/L Gram stain/culture may be positive Drainage required Empyema Pus in pleural space May be free-flowing or multiloculated Gram stain/culture may be positive Drainage required Eventually, fibroblast growth may result in development of thick pleural peel (organizing s tage). Treatment at this stage is difficult and decortication may be required Fig. 35.1 Parapneumonic effusion and empyema: de \201 nition and clinical features. Pleural infection may also occur in the absence of a preceding pneumonic illness ( \200\230 primary empyema \200\231) Clinical features Common - Consider the diagnosis particularly in cases of \200\230slow to respond \200\231 pneumonia, pleural effusion with fever, or high-risk groups with non-spec i \201 c symptoms such as weight loss Similar to clinical presentation of pneumonia: fever, sputum production, chest pain, breathlessness Anaerobic empyema may present less acutely, often with weight loss and without fever. PARAPNEUMONIC EFFUSION AND EMPYEMA 353 Rare - Infected pleural \202 uid may spontaneously drain through the chest wall (empyema necessitatis) or into the lung, leading to a bronchopleural \201 stula and severe pneumonia History of atypical chest pain, vomiting, or oesophageal instrumentation suggests possible underlying oesophageal rupture (measure pleural \202 uid amylase) History of a recent sore throat may suggest Lemierre \200\231s syndrome (acute oropharyngea l infection with Fusobacterium species leads to septic thrombophlebitis of the internal jug ular vein and subsequent metastatic infection and abscess formation, commonly in the lungs and pleura; consider ultrasound of internal jugular vein if suspected); see p 446. Risk factors for developing empyema include diabetes, alcohol abuse, gastro-oesophageal re \202 ux, and intravenous drug abuse. Anaerobic infection is associated particularly with a spiration or poor dental hygiene. Empyema may rarely occur following bronchial obstruction from a tumor or foreign body. Many patients, however, have no apparent risk factors. Differ ential diagnosis includes malignancy, tuberculosis (when the pleural \202 uid is usually lymphocytic), and rheumatoid pleuritis. CHAPTER 35 Pleural effusion 354 Parapneumonic effusion and empyema: bacteriology and investigations Bacteriology - Communit y-acquired infection (% of cases): S. milleri (28%) \200 Anaerobes (19%) \200 S. pneumoniae (14%) \200 Staphylococci (12 %) \200 Other less common organisms include other streptococci, entero- bacteria, H. in \202 uenza, Pseudomonas, TB, and Nocardia. Legionella may very rarely caus e empyema Hospital-acquired infection (% of cases): MRSA (27%) \200 Staphylococci (22%) \200 Enterobacteria (20%) \200 Enterococci (12%) \200 Others include streptococci, Pseudomonas, and anaerobes. Gram-negative organisms may occur in mixed growths with other Gram-negatives or with anaero bes. Investigations - Diagnostic pleural tap is essential if pleural infection is suspected. Frankly purulent or turbid/cloudy pleural \202 uid, organisms on pleural \202 uid Gram stain or culture, or pleural \202 uid pH <7.2 are all indications for chest tube drainage . 40% of pleural infections are culture-negative. Identi \201 cation of anaerobes is impro ved following inoculation of blood culture bottles with pleural \202 uid Ultrasound typically shows echogenic effusion that may be septated, and is useful in guidin g pleural tap in patients with small or loculated effusions or following an unsuccessful \200\230blind \200\231 tap. Very small effusions (<10 mm maximal thickness on ultrasound) p robably do not require tapping and can be observed Contrast-enhanced CT may be useful both in supporting the diagnosis and visualizing the dis tribution of \202 uid. Empyema is associated with pleural enhancement and increased atten uation of extrapleural sub- costal fat. The displacement of adjacent lung by empyema may he lp to distinguish from a parenchymal lung abscess. Empyemas frequently appear lenticular an d may exhibit the \200\230split pleura \200\231 sign of enhancing separated visceral and p arietal pleura. Absence of pleural thickening on CT is unusual in empyema. CT may also some times identify a proximal endobronchial obstructing lesion Blood cultures positive in only 13% of cases, but in these cases they are often the only positive microbiology Bronchoscopy is only indicated if a bronchial obstructing lesion is suspected This page intentionally left blank CHAPTER 35 Pleural effusion 356 Parapneumonic effusion and empyema: management and outcome Management 1. Antibiotics All pa tients with pleural infection should be treated with antibiotics; refer to local hospital p rescribing guidelines. Typical choices: - Community-acquired empyema \200\224second-generat ion cephalosporin (e.g. cefuroxime) plus metronidazole as anaerobic cover. Cipro \202 oxac in and clindamycin together may be appropriate. Add macrolide if Legionella is suspected Hospital-acquired empyema \200\224cover Gram-positive and Gram-negative organisms and anaer obes. MRSA infection is common. Consult with microbiology team. One option is meropenem and vancomycin. Rationalize with culture and sensitivity results (although note that anaerobes are frequent ly dif \201 cult to culture and may coexist with other organisms). Avoid aminoglycosides, which penetrate the pleural space poorly. Switch to oral antibiotics when apyrexial and improving clinically. Co-amoxiclav is a usefu l single agent with anaerobic cover (not if penicillin allergic). Optimal duration of antib iotic treatment unclear, although likely to be at least 3 weeks. 2. Chest tube drainage Indications for chest tube drainage - Frankly purulent or turbid/cloudy pleural \202 uid - Organisms on pleural \202 uid Gram stain or culture - Pleural \202 uid pH <7.2 Consider earlier chest tube drainage in the elderly and patients with comorbidity, and locu lated effusions, as these are associated with a worse outcome.